Subjects -> MEDICAL SCIENCES (Total: 8196 journals)
    - ALLERGOLOGY AND IMMUNOLOGY (205 journals)
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HEMATOLOGY (160 journals)                     

Showing 1 - 151 of 151 Journals sorted alphabetically
Acta Angiologica     Open Access   (Followers: 2)
Acta Haematologica     Full-text available via subscription   (Followers: 23)
Acta Haematologica Polonica     Open Access  
Adipocyte     Open Access  
Advances in Hematology     Open Access   (Followers: 13)
Africa Sanguine     Full-text available via subscription  
American Journal of Hematology     Hybrid Journal   (Followers: 52)
Anemia     Open Access   (Followers: 6)
Annals of Hematology     Hybrid Journal   (Followers: 15)
Archives of Hematology Case Reports and Reviews     Open Access  
Arteriosclerosis, Thrombosis and Vascular Biology     Full-text available via subscription   (Followers: 29)
Artery Research     Hybrid Journal   (Followers: 4)
Artificial Cells, Nanomedicine and Biotechnology     Hybrid Journal   (Followers: 4)
ASAIO Journal     Hybrid Journal   (Followers: 2)
Best Practice & Research Clinical Haematology     Hybrid Journal   (Followers: 5)
Blood     Hybrid Journal   (Followers: 289)
Blood Advances     Open Access   (Followers: 6)
Blood and Lymphatic Cancer : Targets and Therapy     Open Access   (Followers: 7)
Blood Cancer Journal     Open Access   (Followers: 18)
Blood Cells, Molecules, and Diseases     Hybrid Journal   (Followers: 8)
Blood Coagulation & Fibrinolysis     Hybrid Journal   (Followers: 60)
Blood Pressure     Open Access  
Blood Pressure Monitoring     Hybrid Journal   (Followers: 1)
Blood Purification     Full-text available via subscription   (Followers: 6)
Blood Reviews     Hybrid Journal   (Followers: 26)
BMC Hematology     Open Access   (Followers: 7)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 29)
Bone Marrow Transplantation     Hybrid Journal   (Followers: 17)
British Journal of Diabetes & Vascular Disease     Open Access   (Followers: 21)
British Journal of Haematology     Hybrid Journal   (Followers: 60)
British Journal of Primary Care Nursing - Cardiovascular Disease, Diabetes and Kidney Care     Full-text available via subscription   (Followers: 10)
Canadian Journal of Diabetes     Hybrid Journal   (Followers: 28)
Case Reports in Hematology     Open Access   (Followers: 10)
Clinical and Applied Thrombosis/Hemostasis     Open Access   (Followers: 32)
Clinical Diabetes     Full-text available via subscription   (Followers: 39)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 20)
Clinical Lymphoma & Myeloma     Full-text available via subscription   (Followers: 2)
Clinical Lymphoma Myeloma and Leukemia     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Blood Disorders     Open Access   (Followers: 1)
Conquest : The Official Journal of Diabetes Australia     Full-text available via subscription   (Followers: 3)
Current Angiogenesis     Hybrid Journal   (Followers: 1)
Current Diabetes Reports     Hybrid Journal   (Followers: 24)
Current Diabetes Reviews     Hybrid Journal   (Followers: 27)
Current Hematologic Malignancy Reports     Hybrid Journal   (Followers: 2)
Current Opinion in Hematology     Hybrid Journal   (Followers: 20)
Cytotherapy     Full-text available via subscription   (Followers: 2)
Der Diabetologe     Hybrid Journal   (Followers: 2)
Diabetes     Full-text available via subscription   (Followers: 403)
Diabetes aktuell     Hybrid Journal   (Followers: 3)
Diabetes and Vascular Disease Research     Hybrid Journal   (Followers: 20)
Diabetes Care     Full-text available via subscription   (Followers: 461)
Diabetes Case Reports     Open Access  
Diabetes Educator     Hybrid Journal   (Followers: 27)
Diabetes Management     Full-text available via subscription   (Followers: 15)
Diabetes Research and Clinical Practice     Hybrid Journal   (Followers: 71)
Diabetes Spectrum     Full-text available via subscription   (Followers: 16)
Diabetes Technology & Therapeutics     Hybrid Journal   (Followers: 50)
Diabetes Therapy     Open Access   (Followers: 23)
Diabetic Foot & Ankle     Open Access   (Followers: 10)
Diabetic Medicine     Hybrid Journal   (Followers: 142)
Diabetologia     Hybrid Journal   (Followers: 200)
Diabetologia Kliniczna     Hybrid Journal  
Diabetologie und Stoffwechsel     Hybrid Journal   (Followers: 2)
Egyptian Journal of Haematology     Open Access  
eJHaem     Open Access  
European Journal of Haematology     Hybrid Journal   (Followers: 16)
Experimental Hematology     Hybrid Journal   (Followers: 6)
Experimental Hematology & Oncology     Open Access   (Followers: 6)
Expert Review of Hematology     Hybrid Journal   (Followers: 5)
Fluids and Barriers of the CNS     Open Access   (Followers: 1)
Global Journal of Transfusion Medicine     Open Access   (Followers: 1)
Haematologica - the Hematology journal     Open Access   (Followers: 33)
Haemophilia     Hybrid Journal   (Followers: 66)
Hematologia     Full-text available via subscription   (Followers: 3)
Hematología     Open Access  
Hematology     Open Access   (Followers: 15)
Hematology Reports     Open Access   (Followers: 4)
Hematology, Transfusion and Cell Therapy     Open Access   (Followers: 2)
Hematology/Oncology and Stem Cell Therapy     Open Access   (Followers: 6)
Hemodialysis International     Hybrid Journal   (Followers: 3)
Hepatitis Monthly     Open Access   (Followers: 3)
Immunohematology : Journal of Blood Group Serology and Molecular Genetics     Hybrid Journal   (Followers: 1)
Indian Journal of Hematology and Blood Transfusion     Hybrid Journal   (Followers: 2)
Info Diabetologie     Full-text available via subscription   (Followers: 1)
InFo Hämatologie + Onkologie : Interdisziplinäre Fortbildung von Ärzten für Ärzte     Full-text available via subscription  
Integrated Blood Pressure Control     Open Access  
International Blood Research & Reviews     Open Access  
International Journal of Clinical Transfusion Medicine     Open Access   (Followers: 3)
International Journal of Diabetes in Developing Countries     Hybrid Journal   (Followers: 6)
International Journal of Diabetes Research     Open Access   (Followers: 8)
International Journal of Hematologic Oncology     Open Access   (Followers: 2)
International Journal of Hematology     Hybrid Journal   (Followers: 4)
International Journal of Hematology Research     Open Access   (Followers: 2)
International Journal of Hematology-Oncology and Stem Cell Research     Open Access   (Followers: 2)
International Journal of Laboratory Hematology     Hybrid Journal   (Followers: 25)
Iraqi Journal of Hematology     Open Access  
JMIR Diabetes     Open Access  
Journal of Blood Disorders & Transfusion     Open Access   (Followers: 3)
Journal of Applied Hematology     Open Access   (Followers: 2)
Journal of Blood Medicine     Open Access   (Followers: 1)
Journal of Cerebral Blood Flow & Metabolism     Hybrid Journal   (Followers: 3)
Journal of Diabetes     Open Access   (Followers: 20)
Journal of Diabetes and its Complications     Hybrid Journal   (Followers: 25)
Journal of Diabetes and Metabolic Disorders     Open Access   (Followers: 8)
Journal of Diabetes Investigation     Open Access   (Followers: 12)
Journal of Diabetes Mellitus     Open Access   (Followers: 5)
Journal of Diabetes Research     Open Access   (Followers: 13)
Journal of Diabetes Research     Open Access   (Followers: 9)
Journal of Hematological Malignancies     Open Access  
Journal of Hematology     Open Access   (Followers: 2)
Journal of Hematology and Transfusion Medicine     Open Access   (Followers: 1)
Journal of Hematopathology     Hybrid Journal   (Followers: 3)
Journal of Hypo & Hyperglycemia     Partially Free  
Journal of Pediatric Hematology/Oncology     Hybrid Journal   (Followers: 8)
Journal of Social Health and Diabetes     Open Access   (Followers: 1)
Journal of Thrombosis and Haemostasis     Hybrid Journal   (Followers: 80)
Journal of Thrombosis and Thrombolysis     Hybrid Journal   (Followers: 35)
Journal of Transfusion Medicine     Full-text available via subscription  
Kidney and Blood Pressure Research     Open Access   (Followers: 4)
Leukemia     Hybrid Journal   (Followers: 22)
Leukemia and Lymphoma     Hybrid Journal   (Followers: 12)
Leukemia Research     Hybrid Journal   (Followers: 8)
Leukemia Research Reports     Open Access   (Followers: 1)
Leukemia Supplements     Full-text available via subscription  
Mediterranean Journal of Hematology and Infectious Diseases     Open Access  
Nederlands Tijdschrift voor Diabetologie     Hybrid Journal  
Nutrition & Diabetes     Open Access   (Followers: 20)
Oncohematology     Open Access   (Followers: 1)
Open Diabetes Journal     Open Access  
Open Hematology Journal     Open Access   (Followers: 1)
Open Hypertension Journal     Open Access  
Open Journal of Blood Diseases     Open Access  
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 8)
Pediatric Hematology Oncology Journal     Open Access   (Followers: 3)
Peritoneal Dialysis International     Hybrid Journal  
Platelets     Hybrid Journal   (Followers: 3)
Practical Diabetes     Hybrid Journal   (Followers: 7)
Primary Care Diabetes     Hybrid Journal   (Followers: 26)
Research & Reviews : Journal of Oncology and Hematology     Full-text available via subscription   (Followers: 1)
Research and Practice in Thrombosis and Haemostasis     Open Access   (Followers: 1)
Revista Cubana de Hematología, Inmunología y Hemoterapia     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Thrombosis and Hemostasis     Hybrid Journal   (Followers: 45)
Thalassemia Reports     Open Access   (Followers: 1)
The Lancet Haematology     Full-text available via subscription   (Followers: 38)
Therapeutic Advances in Hematology     Hybrid Journal  
Thrombosis & Haemostasis     Hybrid Journal   (Followers: 140)
Thrombosis Research     Hybrid Journal   (Followers: 47)
Transfusionsmedizin - Immunhämatologie, Hämotherapie, Immungenetik, Zelltherapie     Hybrid Journal  
Transplantation and Cellular Therapy     Hybrid Journal   (Followers: 13)
Veins and Lymphatics     Open Access   (Followers: 1)

           

Similar Journals
Journal Cover
Arteriosclerosis, Thrombosis and Vascular Biology
Journal Prestige (SJR): 3.435
Citation Impact (citeScore): 5
Number of Followers: 29  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 1079-5642 - ISSN (Online) 1524-4636
Published by American Heart Association Homepage  [12 journals]
  • Correction to: Macrophage ALDH2 (Aldehyde Dehydrogenase 2) Stabilizing
           Rac2 Is Required for Efferocytosis Internalization and Reduction of
           Atherosclerosis Development

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      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Volume 42, Issue 8, Page e252-e252, August 1, 2022.

      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-27T06:00:02Z
      DOI: 10.1161/ATV.0000000000000156
      Issue No: Vol. 42, No. 8 (2022)
       
  • Expression of CD70 Modulates NO and Redox Status in Endothelial Cells

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      Authors: Arvind K. Pandey Markus Waldeck-Weiermair Quinn S. Wells Wusheng Xiao Shambhu Yadav Emrah Eroglu Thomas Michel Joseph Loscalzo Division of Cardiovascular Medicine; Department of Medicine, Brigham Natural Sciences, Sabanci University, Istanbul, Turkey (E.E.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Endothelial dysfunction is a critical component in the pathogenesis of cardiovascular diseases and is closely associated with NO levels and oxidative stress. Here, we report on novel findings linking endothelial expression of CD70 with alterations in NO and reactive oxygen species.Methods:CD70 expression was genetically manipulated in human aortic and pulmonary artery endothelial cells. Intracellular NO and hydrogen peroxide (H2O2) were measured using genetically encoded biosensors, and cellular phenotypes were assessed.Results:An unbiased phenome-wide association study demonstrated that polymorphisms in CD70 associate with vascular phenotypes. Endothelial cells treated with CD70-directed short-interfering RNA demonstrated impaired wound closure, decreased agonist-stimulated NO levels, and reduced eNOS (endothelial nitric oxide synthase) protein. This was accompanied by reduced NO bioactivity, increased 3-nitrotyrosine levels, and a decrease in the eNOS binding partner heat shock protein 90. Following treatment with the thioredoxin inhibitor auranofin or with agonist histamine, intracellular H2O2levels increased up to 80% in the cytosol, plasmalemmal caveolae, and mitochondria. There was increased expression of NADPH oxidase 1 complex and gp91phox; expression of copper/zinc and manganese superoxide dismutases was also elevated. CD70 knockdown reduced levels of the H2O2scavenger catalase; by contrast, glutathione peroxidase 1 expression and activity were increased. CD70 overexpression enhanced endothelial wound closure, increased NO levels, and attenuated the reduction in eNOS mRNA induced by TNFα.Conclusions:Taken together, these data establish CD70 as a novel regulatory protein in endothelial NO and reactive oxygen species homeostasis, with implications for human vascular disease.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-08-04T09:00:03Z
      DOI: 10.1161/ATVBAHA.122.317866
       
  • Conductance Artery Wall Layers and Their Respective Roles in the Clearance
           Functions

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      Authors: Jean-Baptiste Michel Jeremy Lagrange Veronique Regnault Patrick Lacolley Université de Lorraine; INSERM, DCAC, France.
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Evolutionary organization of the arterial wall into layers occurred concomitantly with the emergence of a highly muscularized, pressurized arterial system that facilitates outward hydraulic conductance and mass transport of soluble substances across the arterial wall. Although colliding circulating cells disperse potential energy within the arterial wall, the different layers counteract this effect: (1) the endothelium ensures a partial barrier function; (2) the media comprises smooth muscle cells capable of endocytosis/phagocytosis; (3) the outer adventitia and perivascular adipocytic tissue are the final receptacles of convected substances. While the endothelium forms a physical and a biochemical barrier, the medial layer is avascular, relying on the specific permeability properties of the endothelium for metabolic support. Different components of the media interact with convected molecules: medial smooth muscle cells take up numerous molecules via scavenger receptors and are capable of phagocytosis of macro/micro particles. The outer layers—the highly microvascularized innervated adventitia and perivascular adipose tissue—are also involved in the clearance functions of the media: the adventitia is the seat of immune response development, inward angiogenesis, macromolecular lymphatic drainage, and neuronal stimulation. Consequently, the clearance functions of the arterial wall are physiologically essential, but also may favor the development of arterial wall pathologies. This review describes how the walls of large conductance arteries have acquired physiological clearance functions, how this is determined by the attributes of the endothelial barrier, governed by endocytic and phagocytic capacities of smooth muscle cells, impacting adventitial functions, and the role of these clearance functions in arterial wall diseases.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-08-04T09:00:03Z
      DOI: 10.1161/ATVBAHA.122.317759
       
  • ILRUNing to Atherosclerosis

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      Authors: Godfrey S. Getz Catherine A. Reardon Department of Pathology; University of Chicago, IL (G.S.G.). Ben May Institute, University of Chicago, IL (C.A.R.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.

      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-08-04T09:00:03Z
      DOI: 10.1161/ATVBAHA.122.318107
       
  • Dietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident
           Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study
           

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      Authors: Meng Wang Zeneng Wang Yujin Lee Heidi T.M. Lai Marcia C. de Oliveira Otto Rozenn N. Lemaitre Amanda Fretts Nona Sotoodehnia Matthew Budoff Joseph A. DiDonato Barbara McKnight W.H. Wilson Tang Bruce M. Psaty David S. Siscovick Stanley L. Hazen Dariush Mozaffarian Friedman School of Nutrition Science; Population Health (B.M.P.), University of Washington, Seattle. Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA (M.B.). The New York Academy of Medicine, New York (D.S.S.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Effects of animal source foods (ASF) on atherosclerotic cardiovascular disease (ASCVD) and underlying mechanisms remain controversial. We investigated prospective associations of different ASF with incident ASCVD and potential mediation by gut microbiota-generated trimethylamine N-oxide, its L-carnitine-derived intermediates γ-butyrobetaine and crotonobetaine, and traditional ASCVD risk pathways.Methods:Among 3931 participants from a community-based US cohort aged 65+ years, ASF intakes and trimethylamine N-oxide-related metabolites were measured serially over time. Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, other atherosclerotic death) was adjudicated over 12.5 years median follow-up. Cox proportional hazards models with time-varying exposures and covariates examined ASF-ASCVD associations; and additive hazard models, mediation proportions by different risk pathways.Results:After multivariable-adjustment, higher intakes of unprocessed red meat, total meat, and total ASF associated with higher ASCVD risk, with hazard ratios (95% CI) per interquintile range of 1.15 (1.01–1.30), 1.22 (1.07–1.39), and 1.18 (1.03–1.34), respectively. Trimethylamine N-oxide-related metabolites together significantly mediated these associations, with mediation proportions (95% CI) of 10.6% (1.0–114.5), 7.8% (1.0–32.7), and 9.2% (2.2–44.5), respectively. Processed meat intake associated with a nonsignificant trend toward higher ASCVD (1.11 [0.98–1.25]); intakes of fish, poultry, and eggs were not significantly associated. Among other risk pathways, blood glucose, insulin, and C-reactive protein, but not blood pressure or blood cholesterol, each significantly mediated the total meat-ASCVD association.Conclusions:In this large, community-based cohort, higher meat intake associated with incident ASCVD, partly mediated by microbiota-derived metabolites of L-carnitine, abundant in red meat. These novel findings support biochemical links between dietary meat, gut microbiome pathways, and ASCVD.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-08-01T09:00:04Z
      DOI: 10.1161/ATVBAHA.121.316533
       
  • Mitochondrial Ca2+ Uptake Drives Endothelial Injury By Radiation Therapy

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      Authors: Karima Ait-Aissa Olha M. Koval Nathanial R. Lindsey Isabella M. Grumbach Abboud Cardiovascular Research Center; Department of Internal Medicine (K.A.A., O.M.K., N.R.L., L.L., I.M.G.), Carver College of Medicine, University of Iowa. Free Radical Radiation Biology Program, Department of Radiation Oncology (I.M.G.), Carver College of Medicine, University of Iowa. Iowa City VA Healthcare System, Iowa City (I.M.G.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Radiation therapy strongly increases the risk of atherosclerotic vascular disease, such as carotid stenosis. Radiation induces DNA damage, in particular in mitochondria, but the upstream and downstream signaling events are poorly understood. The objective of this study was to define such mechanisms.Methods:Endothelial-specific MCU (mitochondrial Ca2+uniporter) knockout and C57Bl6/J mice with or without a preinfusion of a mitoTEMPO (mitochondrial reactive oxygen species [ROS] scavenger) were exposed to a single dose of cranial irradiation. 24, and 240 hours postirradiation, vascular reactivity, endothelial function, and mitochondrial integrity were assessed ex vivo and in vitro.Results:In cultured human endothelial cells, irradiation with 4 Gy increased cytosolic Ca2+transients and the mitochondrial Ca2+concentration ([Ca2+]mt) and activated MCU. These outcomes correlated with increases in mitochondrial ROS (mtROS), loss of NO production, and sustained damage to mitochondrial but not nDNA. Moreover, irradiation impaired activity of the ETC (electron transport chain) and the transcription of ETC subunits encoded by mitochondrial DNA (mtDNA). Knockdown or pharmacological inhibition of MCU blocked irradiation-inducedmtROS production,mtDNA damage, loss of NO production, and impairment of ETC activity. Similarly, the pretreatment with mitoTEMPO, a scavenger ofmtROS, reduced irradiation-induced Ca2+entry, and preserved both the integrity of themtDNA and the production of NO, suggesting a feed-forward loop involving [Ca2+]mandmtROS. Enhancement of DNA repair in mitochondria, but not in the nucleus, was sufficient to block prolongedmtROS elevations and maintain NO production. Consistent with the findings from cultured cells, in C57BL/6J mice, head and neck irradiation decreased endothelium-dependent vasodilation, andmtDNA integrity in the carotid artery after irradiation. These effects were prevented by endothelial knockout of MCU or infusion with mitoTEMPO.Conclusions:Irradiation-induced damage tomtDNA is driven by MCU-dependent Ca2+influx and the generation ofmtROS. Such damage leads to reduced transcription of mitochondrial genes and activity of the ETC, promoting sustainedmtROS production that induces endothelial dysfunction. Our findings suggest that targeting MCU andmtROS might be sufficient to mitigate irradiation-induced vascular disease.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-28T09:00:02Z
      DOI: 10.1161/ATVBAHA.122.317869
       
  • Calcium-Controlled Reactive Oxygen Species Afterburner Perpetuates
           Endothelial Damage After Radiation Therapy

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      Authors: Ralf P. Brandes Ilka Wittig Institute for Cardiovascular Physiology; Goethe-University Frankfurt, Germany. German Center for Cardiovascular Disease DZHK – Partner Site Rhine Main.
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.

      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-28T09:00:02Z
      DOI: 10.1161/ATVBAHA.122.318058
       
  • PLC (Phospholipase C) β2 Promotes VEGF (Vascular Endothelial Growth
           Factor)–Induced Vascular Permeability

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      Authors: Kathryn N. Phoenix Zhichao Yue Lixia Yue Chunxia G. Cronin Bruce T. Liang Luke H. Hoeppner Kevin P. Claffey Center for Vascular Biology; Department of Cell Biology, University of Connecticut Health Center, Farmington. (K.N.P., K.P.C.) Pat Jim Calhoun Cardiology Center, University of Connecticut Health Center, Farmington. (Z.Y., L.Y., C.G.C., B.T.L.) The Hormel Institute, University of Minnesota, Austin (L.H.H.). Masonic Cancer Center, University of Minnesota, Minneapolis (L.H.H.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Regulation of vascular permeability is critical to maintaining tissue metabolic homeostasis. VEGF (vascular endothelial growth factor) is a key stimulus of vascular permeability in acute and chronic diseases including ischemia reperfusion injury, sepsis, and cancer. Identification of novel regulators of vascular permeability would allow for the development of effective targeted therapeutics for patients with unmet medical need.Methods:In vitro and in vivo models of VEGFA-induced vascular permeability, pathological permeability, quantitation of intracellular calcium release and cell entry, and phosphatidylinositol 4,5-bisphosphate levels were evaluated with and without modulation of PLC (phospholipase C) β2.Results:Global knock-out of PLCβ2 in mice resulted in blockade of VEGFA-induced vascular permeability in vivo and transendothelial permeability in primary lung endothelial cells. Further work in an immortalized human microvascular cell line modulated with stable knockdown of PLCβ2 recapitulated the observations in the mouse model and primary cell assays. Additionally, loss of PLCβ2 limited both intracellular release and extracellular entry of calcium following VEGF stimulation as well as reduced basal and VEGFA-stimulated levels of phosphatidylinositol 4,5-bisphosphate compared to control cells. Finally, loss of PLCβ2 in both a hyperoxia-induced lung permeability model and a cardiac ischemia:reperfusion model resulted in improved animal outcomes when compared with wild-type controls.Conclusions:The results implicate PLCβ2 as a key positive regulator of VEGF-induced vascular permeability through regulation of both calcium flux and phosphatidylinositol 4,5-bisphosphate levels at the cellular level. Targeting of PLCβ2 in a therapeutic setting may provide a novel approach to regulating vascular permeability in patients.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-21T09:00:06Z
      DOI: 10.1161/ATVBAHA.122.317645
       
  • High Levels of Complement Activating Enzyme MASP-2 Are Associated With the
           Risk of Future Incident Venous Thromboembolism

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      Authors: Christabel Esi Damoah Omri Snir Kristian Hindberg Peter Garred Judith K. Ludviksen Sigrid K. Brækkan Vânia M. Morelli Tom Eirik Mollnes John-Bjarne Hansen Department of Clinical Medicine; Thrombosis Research Center, UiT The Arctic University of Norway, Tromsø (C.E.D., O.S., K.H., S.K.B., V.M.M., T.E.M., J.-B.H.). Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark (P.G.). Research Laboratory, Nordland Hospital, Bodø, Norway (J.K.L., T.E.M.). Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway (S.K.B., V.M.M., J.-B.H.). Department of Immunology, Oslo University Hospital Technology, Trondheim, Norway (T.E.M.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Experimental studies have shown that the complement activating enzyme MASP-2 (mannose-binding lectin associated serine protease 2) exhibits a thrombin-like activity and that inhibition of MASP-2 protects against thrombosis. In this study, we investigated whether plasma MASP-2 levels were associated with risk of future venous thromboembolism (VTE) and whether genetic variants linked to MASP-2 levels were associated with VTE risk.METHODS:We conducted a population-based nested case-control study involving 410 VTE patients and 842 age- and sex-matched controls derived from the Norwegian Tromsø Study. Logistic regression was used to estimate odds ratios (ORs) of VTE across MASP-2 quartiles. Whole-exome sequencing and protein quantitative trait loci analyses were performed to assess genetic variants associated with MASP-2 levels. A 2-sample Mendelian randomization study, also including data from the INVENT consortium (International Network of Venous Thrombosis), was performed to assess causality.RESULTS:Subjects with plasma MASP-2 in the highest quartile had a 48% higher OR of VTE (OR, 1.48 [95% CI, 1.06–2.06]) and 83% higher OR of deep vein thrombosis (OR, 1.83 [95% CI, 1.23–2.73]) compared with those with MASP-2 levels in the lowest quartile. The protein quantitative trait loci analysis revealed that 3 previously described gene variants, rs12711521 (minor allele frequency, 0.153), rs72550870 (minor allele frequency, 0.045; missense variants in theMASP2gene), and rs2275527 (minor allele frequency, 0.220; exon variant in the adjacentMTORgene) explained 39% of the variation of MASP-2 plasma concentration. The OR of VTE per 1 SD increase in genetically predicted MASP-2 was 1.03 ([95% CI, 1.01–1.05]P=0.0011).CONCLUSIONS:Our findings suggest that high plasma MASP-2 levels are causally associated with risk of future VTE.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-21T09:00:06Z
      DOI: 10.1161/ATVBAHA.122.317746
       
  • Fostering New Scientific Networks in the COVID Era and Beyond

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      Authors: Mabruka Alfaidi Hanrui Zhang Suellen D. Oliveira Department of Internal Medicine; Division of Cardiology, Center for Cardiovascular Diseases Sciences, LSU Health - Shreveport, LA (M.A.). Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York (H.Z.). College of Medicine, Department of Anesthesiology, University of Illinois at Chicago (S.D.O.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Over the last 2 years, the COVID-19 pandemic has stimulated the scientific community by starting a race to develop new vaccines and therapeutic approaches to fight this life-threatening illness. At the same time, the pandemic also evoked an urge for innovative communication strategies to maintain scientific networking and data sharing among investigators. Communication through audiovisual platforms has quickly become a unique tool to sustain scientific interaction, whereas social media has turned into an unmistakable pivotal environment for sharing scientific data and combating misinformation around SARS-CoV-2 infection, prevention, and therapy. Amid this challenging scenario, the scientific community organically established new roles, such as a social media ambassador, a conference-associated role to virtually promote breakthrough science while reconnecting investigators and forging new scientific networks via social media. Moreover, in response to the COVID-19 pandemic, it also became clear the critical need for the scientific community to support efforts to empower flexibility, creativity, and the inclusion of new forms of communication to advance science. Thus, the goal of this brief article is to provide a structured follow-up on the importance for researchers to occupy the internet to promote scientific findings and events, to combat science mistrust by stimulating communication among nonscientists to scientists, and to provide essential strategies for young and senior investigators on how to virtually expand their professional networks within and across research and clinical areas of the cardiovascular field.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-21T09:00:06Z
      DOI: 10.1161/ATVBAHA.122.317452
       
  • ILRUN Promotes Atherosclerosis Through Lipid-Dependent and
           Lipid-Independent Factors

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      Authors: Xin Bi Sylvia Stankov Paul C. Lee Ziyi Wang Xun Wu Li Li Yi-An Ko Lan Cheng Hanrui Zhang Nicholas J. Hand Daniel J. Rader Division of Translational Medicine; Human Genetics, Department of Medicine (X.B., S.S., P.C.L., Y.-A.K., D.J.R.). Cardiovascular Institute (L.L., L.C.). Department of Genetics (X.B., D.J.R.). Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia (D.J.R.). Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York (Z.W., X.W., H.Z.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Common genetic variation in close proximity to theILRUNgene are significantly associated with coronary artery disease as well as with plasma lipid traits. We recently demonstrated that hepatic inflammation and lipid regulator with ubiquitin-associated domain-like and NBR1-like domain (ILRUN) regulates lipoprotein metabolism in vivo in mice. However, whether ILRUN, which is expressed in vascular cells, directly impacts atherogenesis remains unclear. We sought to determine the role of ILRUN in atherosclerosis development in mice.METHODS:For our study, we generated globalIlrundeficient (IlrunKO) male and female mice on 2 hyperlipidemic backgrounds: low density lipoprotein receptor knockout (LdlrKO) and apolipoprotein E knockout (ApoeKO; double knockout [DKO]).RESULTS:Compared with littermate control mice (singleLdlrKO orApoeKO), deletion ofIlrunin DKO mice resulted in significantly attenuated both early and advanced atherosclerotic lesion development, as well as reduced necrotic area. DKO mice also had significantly decreased plasma cholesterol levels, primarily attributable to non-HDL (high-density lipoprotein) cholesterol. Hepatic-specific reconstitution ofILRUNin DKO mice on theApoeKO background normalized plasma lipids, but atherosclerotic lesion area and necrotic area remained reduced in DKO mice. Further analysis showed that loss ofIlrunincreased efferocytosis receptor MerTK expression in macrophages, enhanced in vitro efferocytosis, and significantly improved in situ efferocytosis in advanced lesions.CONCLUSIONS:Our results support ILRUN as an important novel regulator of atherogenesis that promotes lesion progression and necrosis. It influences atherosclerosis through both plasma lipid-dependent and lipid-independent mechanisms. These findings support ILRUN as the likely causal gene responsible for genetic association of variants with coronary artery disease at this locus and suggest that suppression of ILRUN activity might be expected to reduce atherosclerosis.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-14T12:00:01Z
      DOI: 10.1161/ATVBAHA.121.317156
       
  • Limited Effect of Y Chromosome Variation on Coronary Artery Disease and
           Mortality in UK Biobank

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      Authors: Paul R.H.J. Timmers James F. Wilson MRC Human Genetics Unit; MRC Institute of Genetics Cancer, University of Edinburgh, United Kingdom. (P.R.H.J.T., J.F.W.) Centre for Global Health Research, Usher Institute, University of Edinburgh, United Kingdom. (P.R.H.J.T., J.F.W.)
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:The effect of genetic variation in the male-specific region of the Y chromosome (MSY) on coronary artery disease and cardiovascular risk factors has been disputed. In this study, we systematically assessed the association of MSY genetic variation on these traits using a kin-cohort analysis of family disease history in the largest sample to date.Methods:We tested 90 MSY haplogroups against coronary artery disease, hypertension, blood pressure, classical lipid levels, and all-cause mortality in up to 152 186 unrelated, genomically British individuals from UK Biobank. Unlike previous studies, we did not adjust for heritable lifestyle factors (to avoid collider bias) and instead adjusted for geographic variables and socioeconomic deprivation, given the link between MSY haplogroups and geography. For family history traits, subject MSY haplogroups were tested against father and mother disease as validation and negative control, respectively.Results:Our models find little evidence for an effect of any MSY haplogroup on cardiovascular risk in participants. Parental models confirm these findings.Conclusions:Kin-cohort analysis of the Y chromosome uniquely allows for discoveries in subjects to be validated using family history data. Despite our large sample size, improved models, and parental validation, there is little evidence to suggest cardiovascular risk in UK Biobank is influenced by genetic variation in MSY.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-14T12:00:01Z
      DOI: 10.1161/ATVBAHA.122.317664
       
  • Thromboinflammation: From Atherosclerosis to COVID-19

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      Authors: Denisa D. Wagner Lukas A. Heger Cellular; Molecular Medicine, Boston Children’s Hospital/Harvard Medical School, MA (D.D.W.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      The activating interplay of thrombosis and inflammation (thromboinflammation) has been established as a major underlying pathway, driving not only cardiovascular disease but also autoimmune disease and most recently, COVID-19. Throughout the years, innate immune cells have emerged as important modulators of this process. As the most abundant white blood cell in humans, neutrophils are well-positioned to propel thromboinflammation. This includes their ability to trigger an organized cell death pathway with the release of decondensed chromatin structures called neutrophil extracellular traps. Decorated with histones and cytoplasmic and granular proteins, neutrophil extracellular traps exert cytotoxic, immunogenic, and prothrombotic effects accelerating disease progression. Distinct steps leading to extracellular DNA release (NETosis) require the activities of PAD4 (protein arginine deiminase 4) catalyzing citrullination of histones and are supported by neutrophil inflammasome. By linking the immunologic function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets, PAD4 activity holds important implications for understanding the processes that fuel thromboinflammation. We will also discuss mechanisms whereby vascular occlusion in thromboinflammation depends on the interaction of neutrophil extracellular traps with ultra-large VWF (von Willebrand Factor) and speculate on the importance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thromboinflammatory diseases including atherosclerosis and COVID-19.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-08T01:17:11Z
      DOI: 10.1161/ATVBAHA.122.317162
       
  • Embryologic Origin Influences Smooth Muscle Cell Phenotypic Modulation
           Signatures in Murine Marfan Syndrome Aortic Aneurysm

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      Authors: Albert J. Pedroza Alex R. Dalal Rohan Shad Nobu Yokoyama Ken Nakamura Paul Cheng Robert C. Wirka Olivia Mitchel Michael Baiocchi William Hiesinger Thomas Quertermous Michael P. Fischbein Department of Cardiothoracic Surgery; Stanford University School of Medicine, CA. (A.J.P., A.R.D., R.S., N.Y., K.N., W.H., M.P.F.) Division of Cardiovascular Medicine, Stanford University School of Medicine, CA. (P.C., T.Q.) Department of Epidemiology Population Health, Stanford University School of Medicine, CA. (M.B.) Division of Cardiology, UNC School of Medicine, Chapel Hill, NC (R.C.W.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Aortic root smooth muscle cells (SMC) develop from both the second heart field (SHF) and neural crest. Disparate responses to disease-causingFbn1variants by these lineages are proposed to promote focal aortic root aneurysm formation in Marfan syndrome (MFS), but lineage-stratified SMC analysis in vivo is lacking.Methods:We generated SHF lineage-traced MFS mice and performed integrated multiomic (single-cell RNA and assay for transposase-accessible chromatin sequencing) analysis stratified by embryological origin. SMC subtypes were spatially identified via RNA in situ hybridization. Response toTWIST1overexpression was determined via lentiviral transduction in human aortic SMCs.Results:Lineage stratification enabled nuanced characterization of aortic root cells. We identified heightened SHF-derived SMC heterogeneity including a subset ofTnnt2-expressing cells distinguished by altered proteoglycan expression. MFS aneurysm-associated SMC phenotypic modulation was identified in both SHF-traced and nontraced (neural crest–derived) SMCs; however, transcriptomic responses were distinct between lineages. SHF-derived modulated SMCs overexpressed collagen synthetic genes and small leucine-rich proteoglycans while nontraced SMCs activated chondrogenic genes. These modulated SMCs clustered focally in the aneurysmal aortic root at the region of SHF/neural crest lineage overlap. Integrated RNA-assay for transposase-accessible chromatin analysis identified enrichedTwist1andSmad2/3/4complex binding motifs in SHF-derived modulated SMCs. TWIST1 overexpression promoted collagen andSLRPgene expression in vitro, suggesting TWIST1 may drive SHF-enriched collagen synthesis in MFS aneurysm.Conclusions:SMCs derived from both SHF and neural crest lineages undergo phenotypic modulation in MFS aneurysm but are defined by subtly distinct transcriptional responses. Enhanced TWIST1 transcription factor activity may contribute to enriched collagen synthetic pathways SHF-derived SMCs in MFS.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-07T09:00:03Z
      DOI: 10.1161/ATVBAHA.122.317381
       
  • Microarchitectural Changes of Cardiovascular Calcification in Response to
           In Vivo Interventions Using Deep-Learning Segmentation and Computed
           Tomography Radiomics

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      Authors: Nikhil Rajesh Patel Kulveer Setya Stuti Pradhan Mimi Lu Linda L. Demer Yin Tintut Department of Medicine, University of California, Los Angeles. (N.R.P; K.S, S.P, M.L, L.L.D, Y.T.) Department of Bioengineering, University of California, Los Angeles. (L.L.D.) Department of Physiology, University of California, Los Angeles. (L.L.D, Y.T.) Department of Orthopaedic Surgery, University of California, Los Angeles. (Y.T.) VA Greater Los Angeles Healthcare System, CA (L.L.D, Y.T.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Coronary calcification associates closely with cardiovascular risk, but its progress is accelerated in response to some interventions widely used to reduce risk. This paradox suggests that qualitative, not just quantitative, changes in calcification may affect plaque stability. To determine if the microarchitecture of calcification varies with aging, Western diet, statin therapy, and high intensity, progressive exercise, we assessed changes in a priori selected computed tomography radiomic features (intensity, size, shape, and texture).METHODS:Longitudinal computed tomography scans of mice (Apoe−/−) exposed to each of these conditions were autosegmented by deep learning segmentation, and radiomic features of the largest deposits were analyzed.RESULTS:Over 20 weeks of aging, intensity and most size parameters increased, but surface-area-to-volume ratio (a measure of porosity) decreased, suggesting stabilization. However, texture features (coarseness, cluster tendency, and nonuniformity) increased, suggesting heterogeneity and likely destabilization. Shape parameters showed no significant changes, except sphericity, which showed a decrease. The Western diet had significant effects on radiomic features related to size and texture, but not intensity or shape. In mice undergoing either pravastatin treatment or exercise, the selected radiomic features of their computed tomography scans were not significantly different from those of their respective controls. Interestingly, the total number of calcific deposits increased significantly less in the 2 intervention groups compared with the respective controls, suggesting more coalescence and/or fewer de novo deposits.CONCLUSIONS:Thus, aging and standard interventions alter the microarchitectural features of vascular calcium deposits in ways that may alter plaque biomechanical stability.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-16T09:00:26Z
      DOI: 10.1161/ATVBAHA.122.317761
       
  • Epicardial Adipose Tissue Ceramides Are Related to Lipoprotein Lipase
           Activity in Coronary Artery Disease: Unfolding a Missing Link

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      Authors: Magalí Barchuk Patricia Ancel Verónica Miksztowicz Elisa Doukbi Ljubica Svilar Daniel Yñón Juan Patricio Nogueira Miguel Rubio Laura Schreier Anne Dutour Jean Charles Martin Bénédicte Gaborit Gabriela Berg Universidad de Buenos Aires; Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina (M.B., L.S., G.B.). Aix-Marseille University, INSERM, INRAE, C2VN, France (P.A., E.D., L.S., A.D., J.C.M., B.G.). Endocrinology, Metabolic Diseases Nutrition Department, Assistance Publique Hôpitaux de Marseille, France (A.D., B.G.). CRIBIOM, Criblage Biologique Marseille, Faculté de Medecine de la Timone, France (L.S.). Universidad de Buenos Aires, CONICET, Facultad de Farmacia y Bioquímica, Argentina (M.B., V.M., G.B.). Universidad de Buenos Aires, Hospital de Clínicas “José de San Martín”, División de Cirugía Cardiovascular, Argentina (D.Y., M.R.). Servicio de Docencia e Investigación, Hospital Central de Formosa, Facultad de Ciencias de la Salud, Universidad Nacional de Formosa, Argentina (J.P.N.).
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Epicardial adipose tissue (EAT) contributes to coronary artery disease (CAD). EAT presents a specific lipidomic signature, showing increased ceramides and other proinflammatory lipids content. Besides, LPL (lipoprotein lipase) activity in EAT would contribute to its expansion, supplying fatty acids to the tissue. Our aim was to evaluate the relations between LPL activity, regulators of LPL, and ceramides in EAT from CAD patients.Methods:We studied patients undergoing coronary bypass graft (CAD, n=25) and patients without CAD (no CAD, n=14). EAT and subcutaneous AT (SAT) were obtained, tissue LPL activity and its regulator’s expression (ANGPTL4, GPIHBP1 [glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1], and PPARγ [peroxisomal proliferator–activated receptor γ]) were assessed. Tissue lipidomes were evaluated by UHPLC-MS, in positive and negative ionization modes.Results:LPL activity was higher in EAT from CAD (P<0.001), and in EAT than SAT in both groups (P<0.001). ANGPTL4 levels were lower, GPIHBP1 and PPARγ levels were higher in EAT from CAD (P<0.001). In both groups, EAT exhibited more ceramide (P=0.01), directly associated with LPL activity, being the strongest association with Cer18:1/24:1 (P<0.001). EAT Cer18:1/16:0 to Cer18:1/24:0 and Cer18:1/24:1 to 18:1/24:0 ratios were higher in CAD (P=0.03;P<0.001, respectively), the latter directly associated with LPL activity (r=0.63,P<0.001) GPIHBP1 levels (r=0.68,P<0.001), and inversely to EAT ANGPTL4 expression (r=−0.49,P=0.03). Pairwise partial correlation network showed associations among bioactive lipids and LPL and its regulators (P<0.001 in all cases).Conclusions:The association between LPL activity, total ceramide, and the atherogenic ceramide ratios highlights the importance of the enzyme and these bioactive lipids contributing to the different metabolic profile of EAT in CAD.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-16T09:00:26Z
      DOI: 10.1161/ATVBAHA.122.317840
       
  • Dissecting the Heterogeneity of Human Thoracic Aortic Aneurysms Using
           Single-Cell Transcriptomics

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      Authors: Dogukan Mizrak Hao Feng Bo Yang Department of Cardiac Surgery, University of Michigan, Ann Arbor (D.M; H.F, B.Y.). Xiangya School of Medicine, Central South University, Changsha, China (H.F.).
      First page: 919
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Thoracic aortic aneurysm is a life-threatening condition caused by weakening of the thoracic aorta wall, often developing silently until dissection or rupture occurs. Despite substantial efforts in the past decade, there have been no significant therapeutic advances to prevent or clinically manage diverse forms of thoracic aortic aneurysm and dissection with the only effective treatment being surgical repair. There is an urgent need to understand intra- and inter-aneurysmal heterogeneity underlying thoracic aortic aneurysm and dissection pathogenesis. The human aortic wall consists of many cell types and exhibits significant regional heterogeneity. High-throughput single-cell RNA sequencing has emerged as the principal tool to reveal the complexity in human tissues and clinical specimens. Recent single-cell RNA sequencing studies of different aortic cell populations both in vivo and in vitro began to dissect this complexity and have provided valuable information. In this review, we summarize these findings and discuss the potential applications of single-cell transcriptomics and related high-content technologies in human thoracic aortic aneurysm and dissection research, as well as the challenges associated with it.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-16T09:00:26Z
      DOI: 10.1161/ATVBAHA.122.317484
       
  • Fibrinogen and Factor XIII in Venous Thrombosis and Thrombus Stability

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      Authors: Alisa S. Wolberg Yaqiu Sang Department of Pathology; UNC Blood Research Center, University of North Carolina, Chapel Hill.
      First page: 931
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      As the third most common vascular disease, venous thromboembolism is associated with significant mortality and morbidity. Pathogenesis underlying venous thrombosis is still not fully understood. Accumulating data suggest fibrin network structure and factor XIII-mediated crosslinking are major determinants of venous thrombus mass, composition, and stability. Understanding the cellular and molecular mechanisms mediating fibrin(ogen) and factor XIII production and function and their ability to influence venous thrombogenesis and resolution may inspire new anticoagulant strategies that target these proteins to reduce or prevent venous thrombosis in certain at-risk patients. This article summarizes fibrinogen and factor XIII biology and current knowledge of their function during venous thromboembolism.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-02T09:00:07Z
      DOI: 10.1161/ATVBAHA.122.317164
       
  • Dichotomous Roles of Smooth Muscle Cell–Derived MCP1 (Monocyte
           Chemoattractant Protein 1) in Development of Atherosclerosis

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      Authors: Katherine M. Owsiany Rebecca A. Deaton Karen G. Soohoo Anh Tram Nguyen Gary K. Owens University of Virginia School of Medicine, Charlottesville (K.M.O.). Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville (K.M.O; R.A.D, G.K.O.). Eastern Virginia Medical School, Norfolk (K.G.S.). Duke University School of Medicine, Durham, NC (A.T.N.).
      First page: 942
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Smooth muscle cells (SMCs) in atherosclerotic plaque take on multiple nonclassical phenotypes that may affect plaque stability and, therefore, the likelihood of myocardial infarction or stroke. However, the mechanisms by which these cells affect stability are only beginning to be explored.METHODS:In this study, we investigated the contribution of inflammatory MCP1 (monocyte chemoattractant protein 1) produced by both classical Myh11 (myosin heavy chain 11)+SMCs and SMCs that have transitioned through an Lgals3 (galectin 3)+state in atherosclerosis using smooth muscle lineage tracing mice that label all Myh11+cells and a dual lineage tracing system that targets Lgals3-transitioned SMC only.RESULTS:We show that loss of MCP1 in all Myh11+smooth muscle results in a paradoxical increase in plaque size and macrophage content, driven by a baseline systemic monocytosis early in atherosclerosis pathogenesis. In contrast, knockout of MCP1 in Lgals3-transitioned SMCs using a complex dual lineage tracing system resulted in lesions with an increased Acta2 (actin alpha 2, smooth muscle)+fibrous cap and decreased investment of Lgals3-transitioned SMCs, consistent with increased plaque stability. Finally, using flow cytometry and single-cell RNA sequencing, we show that MCP1 produced by Lgals3-transitioned SMCs influences multiple populations of inflammatory cells in late-stage plaques.CONCLUSIONS:MCP1 produced by classical SMCs influences monocyte levels beginning early in disease and was atheroprotective, while MCP1 produced by the Lgals3-transitioned subset of SMCs exacerbated plaque pathogenesis in late-stage disease. Results are the first to determine the function of Lgals3-transitioned inflammatory SMCs in atherosclerosis and highlight the need for caution when considering therapeutic interventions involving MCP1.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-23T09:00:03Z
      DOI: 10.1161/ATVBAHA.122.317882
       
  • Lgals3-Transitioned Inflammatory Smooth Muscle Cells: Major Regulators of
           Atherosclerosis Progression and Inflammatory Cell Recruitment

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      Authors: Sizhao Lu Mary C.M. Weiser-Evans Department of Medicine; Division of Renal Diseases Translation, University of Colorado Anschutz Medical Campus, Aurora. (M.C.M.W.-E.) Department of Medicine, Cardiovascular Pulmonary Research Program, University of Colorado Anschutz Medical Campus, Aurora. (M.C.M.W.-E.)
      First page: 957
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.

      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-07-07T09:00:03Z
      DOI: 10.1161/ATVBAHA.122.318009
       
  • Identification of a Distinct Platelet Phenotype in the Elderly: ADP
           Hypersensitivity Coexists With Platelet PAR (Protease-Activated
           Receptor)-1 and PAR-4–Mediated Thrombin Resistance

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      Authors: Sonali R. Gnanenthiran Gabrielle J. Pennings Caroline J. Reddel Heather Campbell Maaike Kockx Justin R. Hamilton Vivien Chen Leonard Kritharides Cardiology Department; Concord Repatriation General Hospital, NSW, Australia (S.R.G., M.K., L.K.). ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Sydney, NSW, Australia (S.R.G., G.J.P., C.J.R., H.C., M.K., V.C., L.K.). Australian Centre of Blood Diseases, Monash University, Victoria, Australia (J.R.H.). Haematology Department, Concord Repatriation General Hospital, NSW, Australia (V.C.).
      First page: 960
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Thrombin (via PAR [protease-activated receptor]-1 and PAR-4) and ADP (via P2Y12receptors) are potent endogenous platelet activators implicated in the development of cardiovascular disease. We aimed to assess whether platelet pathways alter with aging.Methods:We characterized platelet activity in community-dwelling volunteers (n=174) in the following age groups: (1) 20 to 30 (young); (2) 40 to 55 (middle-aged); (3) ≥70 years (elderly). Platelet activity was assessed by aggregometry; flow cytometry (surface markers [P-selectin: alpha granule release, CD63: dense granule release, PAC-1 (measure of conformationally active GPIIb/IIIa at the fibrinogen binding site): GPIIb/IIIa conformational activation] measured under basal conditions and after agonist stimulation [ADP, thrombin, PAR-1 agonist or PAR-4 agonist]); receptor cleavage and quantification; fluorometry; calcium flux; ELISA.Results:The elderly had higher basal platelet activation than the young, evidenced by increased expression of P-selectin, CD63, and PAC-1, which correlated with increasing inflammation (IL [interleukin]-1β/IL-6). The elderly demonstrated higher P2Y12receptor density, with greater ADP-induced platelet aggregation (P<0.05). However, elderly subjects were resistant to thrombin, achieving less activation in response to thrombin (higher EC50) and to selective stimulation of both PAR-1 and PAR-4, with higher basal PAR-1/PAR-4 cleavage and less inducible PAR-1/PAR-4 cleavage (allP<0.05). Thrombin resistance was attributable to a combination of reduced thrombin orienting receptor GPIbα, reduced secondary ADP contribution to thrombin-mediated activation, and blunted calcium flux. D-Dimer, a marker of in situ thrombin generation, correlated with platelet activation in the circulation, ex vivo thrombin resistance, and circulating inflammatory mediators (TNF [tumor necrosis factor]-α/IL-6).Conclusions:Aging is associated with a distinctive platelet phenotype of increased basal activation, ADP hyperreactivity, and thrombin resistance. In situ thrombin generation associated with systemic inflammation may be novel target to prevent cardiovascular disease in the elderly.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-16T09:00:26Z
      DOI: 10.1161/ATVBAHA.120.316772
       
  • Evolving Mural Defects, Dilatation, and Biomechanical Dysfunction in
           Angiotensin II–Induced Thoracic Aortopathies

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      Authors: Dar Weiss Aaron S. Long George Tellides Stéphane Avril Jay D. Humphrey Matthew R. Bersi Department of Biomedical Engineering; Yale University, New Haven, CT. (D.W., A.S.L., J.D.H., M.R.B.) Department of Surgery, Yale University, New Haven, CT. (G.T.) Vascular Biology Materials Science, Washington University in St. Louis, MO (M.R.B.).
      First page: 973
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Thoracic aortopathy associates with extracellular matrix remodeling and altered biomechanical properties. We sought to quantify the natural history of thoracic aortopathy in a common mouse model and to correlate measures of wall remodeling such as aortic dilatation or localized mural defects with evolving microstructural composition and biomechanical properties of the wall.METHODS:We combined a high-resolution multimodality imaging approach (panoramic digital image correlation and optical coherence tomography) with histopathologic examinations and biaxial mechanical testing to correlate spatially, for the first time, macroscopic mural defects and medial degeneration within the ascending aorta with local changes in aortic wall composition and mechanical properties.RESULTS:Findings revealed strong correlations between local decreases in elastic energy storage and increases in circumferential material stiffness with increasing proximal aortic diameter and especially mural defect size. Mural defects tended to exhibit a pronounced biomechanical dysfunction that is driven by an altered organization of collagen and elastic fibers.CONCLUSIONS:While aneurysmal dilatation is often observed within particular segments of the aorta, dissection and rupture initiate as highly localized mechanical failures. We show that wall composition and material properties are compromised in regions of local mural defects, which further increases the dilatation and overall structural vulnerability of the wall. Identification of therapies focused on promoting robust collagen accumulation may protect the wall from these vulnerabilities and limit the incidence of dissection and rupture.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-30T09:00:02Z
      DOI: 10.1161/ATVBAHA.122.317394
       
  • PIKfyve-Dependent Phosphoinositide Dynamics in Megakaryocyte/Platelet
           Granule Integrity and Platelet Functions

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      Authors: Manuella Caux Rana Mansour Jean-Marie Xuereb Gaëtan Chicanne Julien Viaud Alicia Vauclard Frédéric Boal Bernard Payrastre Hélène Tronchère Sonia Severin INSERM U1297; I2MC Université Paul Sabatier, Toulouse, France (M.C., R.M., J.-M.X., G.C., J.V., A.V., F.B., B.P., H.T., S.S.). CHU de Toulouse, Laboratoire d’Hématologie, Toulouse, France (B.P.).
      First page: 987
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Secretory granules are key elements for platelet functions. Their biogenesis and integrity are regulated by fine-tuned mechanisms that need to be fully characterized. Here, we investigated the role of the phosphoinositide 5-kinase PIKfyve and its lipid products, PtdIns5P (phosphatidylinositol 5 monophosphate) and PtdIns(3,5)P2(phosphatidylinositol (3,5) bisphosphate) in granule homeostasis in megakaryocytes and platelets.METHODS:For that, we invalidated PIKfyve by pharmacological inhibition or gene silencing in megakaryocytic cell models (human MEG-01 cell line, human imMKCLs, mouse primary megakaryocytes) and in human platelets.RESULTS:We unveiled that PIKfyve expression and its lipid product levels increased with megakaryocytic maturation. In megakaryocytes, PtdIns5P and PtdIns(3,5)P2were found in alpha and dense granule membranes with higher levels in dense granules. Pharmacological inhibition or knock-down of PIKfyve in megakaryocytes decreased PtdIns5P and PtdIns(3,5)P2synthesis and induced a vacuolar phenotype with a loss of alpha and dense granule identity. Permeant PtdIns5P and PtdIns(3,5)P2and the cation channel TRPML1 (transient receptor potential mucolipins) and TPC2 activation were able to accelerate alpha and dense granule integrity recovery following release of PIKfyve pharmacological inhibition. In platelets, PIKfyve inhibition specifically impaired the integrity of dense granules culminating in defects in their secretion, platelet aggregation, and thrombus formation.CONCLUSIONS:These data demonstrated that PIKfyve and its lipid products PtdIns5P and PtdIns(3,5)P2control granule integrity both in megakaryocytes and platelets.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-16T09:00:26Z
      DOI: 10.1161/ATVBAHA.122.317559
       
  • Preventing Cholesterol-Induced Perk (Protein Kinase RNA-Like Endoplasmic
           Reticulum Kinase) Signaling in Smooth Muscle Cells Blocks Atherosclerotic
           Plaque Formation

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      Authors: Abhijnan Chattopadhyay Pujun Guan Suravi Majumder Kaveeta Kaw Zhen Zhou Chen Zhang Siddharth K. Prakash Anita Kaw L. Maximillian Buja Callie S. Kwartler Dianna M. Milewicz Division of Medical Genetics; Department of Internal Medicine, McGovern Medical School The University of Texas Health Science Center at Houston (A.C., P.G., S.M., K.K., Z.Z., A.K., C.S.K., D.M.M.). Department of Pathology UTHealth, Houston (P.G.). Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (C.Z.). Department of Cardiovascular Surgery, Texas Heart Institute, Houston (C.Z.).
      First page: 1005
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.METHODS:We generated an SMC-specificPerkknockout mouse model, induced hyperlipidemia in the mice by AAV-PCSK9DYinjection, and subjected them to a high-fat diet. We then assessed atherosclerotic plaque formation and performed single-cell transcriptomic studies using aortic tissue from these mice.RESULTS:SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 clusters of modulated SMCs in hyperlipidemic mice, one of which is absent whenPerkis deleted in SMCs. The 2 modulated SMC clusters have significant overlap of transcriptional changes, but the Perk-dependent cluster uniquely shows a global decrease in the number of transcripts, a marker of an integrated stress response. SMC-specific Perk deletion also prevents migration of both contractile and modulated SMCs from the medial layer of the aorta.CONCLUSIONS:Our results indicate that hypercholesterolemia drives both Perk-dependent and Perk-independent SMC modulation and that deficiency of Perk significantly blocks atherosclerotic plaque formation.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-16T09:00:26Z
      DOI: 10.1161/ATVBAHA.121.317451
       
  • ENPP2 (Endothelial Ectonucleotide Pyrophosphatase/Phosphodiesterase 2)
           Increases Atherosclerosis in Female and Male Mice

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      Authors: Ela Karshovska Rokia Mohibullah Mengyu Zhu Farima Zahedi Dominique Thomas Christiana Magkrioti Claudia Geissler Remco T.A. Megens Mariaelvy Bianchini Maliheh Nazari-Jahantigh Nerea Ferreirós Vassilis Aidinis Andreas Schober Institute for Cardiovascular Prevention; Ludwig-Maximilians-University, Munich, Germany (E.K., R.M., M.Z., F.Z., C.G., R.T.A.M., M.B., M.N.-J., A.S.). Now with Department of Biomedical Science Pharmacology, Frankfurt, Germany (D.T.). Division of Immunology, Biomedical Science Research, Center Alexander Fleming, Athens, Greece (C.M., V.A.). Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands (M.Z., R.T.A.M.). German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, Germany (M.N.-J., A.S.).
      First page: 1023
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Maladapted endothelial cells (ECs) secrete ENPP2 (ectonucleotide pyrophosphatase/phosphodiesterase 2; autotaxin)—a lysophospholipase D that generates lysophosphatidic acids (LPAs). ENPP2 derived from the arterial wall promotes atherogenic monocyte adhesion induced by generating LPAs, such as arachidonoyl-LPA (LPA20:4), from oxidized lipoproteins. Here, we aimed to determine the role of endothelial ENPP2 in the production of LPAs and atherosclerosis.METHODS:We quantified atherosclerosis in mice harboring loxP-flankedEnpp2alleles crossed withApoe–/–mice expressing tamoxifen-inducible Cre recombinase under the control of the EC-specific bone marrow X kinase promoter after 12 weeks of high-fat diet feeding.RESULTS:A tamoxifen-induced EC-specificEnpp2knockout decreased atherosclerosis, accumulation of lesional macrophages, monocyte adhesion, and expression of endothelial CXCL (C-X-C motif chemokine ligand) 1 in male and femaleApoe–/–mice. In vitro, ENPP2 mediated the mildly oxidized LDL (low-density lipoprotein)-induced expression of CXCL1 in aortic ECs by generating LPA20:4, palmitoyl-LPA (LPA16:0), and oleoyl-LPA (LPA18:1). ENPP2 and its activity were detected on the endothelial surface by confocal imaging. The expression of endothelialEnpp2established a strong correlation between the plasma levels of LPA16:0, stearoyl-LPA (LPA18:0), and LPA18:1 and plaque size and a strong negative correlation between the LPA levels and ENPP2 activity in the plasma. Moreover, endothelialEnpp2knockout increased the weight of high-fat diet–fed maleApoe–/–mice.CONCLUSIONS:We demonstrated that the expression of ENPP2 in ECs promotes atherosclerosis and endothelial inflammation in a sex-independent manner. This might be due to the generation of LPA20:4, LPA16:0, and LPA18:1 from mildly oxidized lipoproteins on the endothelial surface.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-16T09:00:26Z
      DOI: 10.1161/ATVBAHA.122.317682
       
  • pH-Dependent Protonation of Histidine Residues Is Critical for
           Electrostatic LDL (Low-Density Lipoprotein) Binding to Human Coronary
           Arteries

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      Authors: Lars Glise Mikael Rutberg Liliana Håversen Malin C. Levin Max Levin Anders Jeppsson Jan Borén Per Fogelstrand Department of Molecular; Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden (L.G., M.R., L.H., M.C.L., M.L., A.J., J.B., P.F.). Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden (A.J.). Sahlgrenska University Hospital/Wallenberg Laboratory, Gothenburg, Sweden (J.B.).
      First page: 1037
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:The initiating step in atherogenesis is the electrostatic binding of LDL (low-density lipoprotein) to proteoglycan glycosaminoglycans in the arterial intima. However, although proteoglycans are widespread throughout the intima of most coronary artery segments, LDL is not evenly distributed, indicating that LDL retention is not merely dependent on the presence of proteoglycans. We aim to identify factors that promote the interaction between LDL and the vessel wall of human coronary arteries.Methods:We developed an ex vivo model to investigate binding of human-labeled LDL to human coronary artery sections without the interference of cellular processes.Results:By staining consecutive sections of human coronary arteries, we found strong staining of sulfated glycosaminoglycans throughout the arterial intima, whereas endogenous LDL deposits were focally distributed. Ex vivo binding of LDL was uniform in all intimal areas with sulfated glycosaminoglycans. However, lowering the pH from 7.4 to 6.5 triggered a 35-fold increase in LDL binding. The pH-dependent binding was abolished by pretreating LDL with diethyl-pyrocarbonate, which blocks the protonation of histidine residues, or cyclohexanedione, which inhibits the positive charge of site B on LDL. Thus, both histidine protonation and site B are required for strong electrostatic LDL binding to the intima.Conclusions:This study identifies histidine protonation as an important component for electrostatic LDL binding to human coronary arteries. Our findings show that the local pH will have a profound impact on LDL’s affinity for sulfated glycosaminoglycans, which may influence the retention and accumulation pattern of LDL in the arterial vasculature.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-02T09:00:07Z
      DOI: 10.1161/ATVBAHA.122.317868
       
  • Microcalcification and Thoracic Aortopathy: A Window Into Disease Severity

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      Authors: Alexander J. Fletcher Jennifer Nash Maaz Syed Mark G. Macaskill Adriana A.S. Tavares Niki Walker Hannah Salcudean Jonathon A. Leipsic Kelvin Lim Jillian Madine William Wallace Mark Field David E. Newby Rihab Bouchareb Michael Seidman Riaz Akhtar Stephanie Sellers British Heart Foundation Centre for Cardiovascular Science; University of Edinburgh, United Kingdom. (A.J.F., J.N., M.S., N.W., D.E.N.) Edinburgh Imaging Facility, Queens Medical Research Institute, University of Edinburgh, United Kingdom. (M.G.M., A.A.S.T.) Division of Pathology, University of Edinburgh, United Kingdom. (W.W.) Scottish Adult Congenital Cardiology Service, Golden Jubilee National Hospital, Clydebank, Glasgow, United Kingdom (N.W.). Department of Radiology, Division of Cardiology, Cardiovascular Translational Lab at the Centre for Heart Lung Innovation, St. Paul’s Hospital Pathobiology, Toronto General Hospital, Canada (M.S.).
      First page: 1048
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      BACKGROUND:Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established.METHODS:One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography.RESULTS:Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71–10.39];P≤0.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87–11.80];P<0.042) compared with control samples (n=18; 0.79 [0.36–1.90]). Alkaline phosphatase (n=26;P=0.0019) and OPN (osteopontin; n=26;P=0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman ρ, −0.51;P<0.0001)—a process closely linked with elastin loss (n=82; Spearman ρ, −0.43;P<0.0001) and lower tissue elastic modulus (n=28; Spearman ρ, 0.43;P=0.026).18F-sodium fluoride autoradiography demonstrated good correlation with histologically quantified microcalcification (n=66; r=0.76;P<0.001) and identified areas of focal weakness in vivo.CONCLUSIONS:Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification.18F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-30T09:00:02Z
      DOI: 10.1161/ATVBAHA.122.317111
       
  • Aging Alters the Aortic Proteome in Health and Thoracic Aortic Aneurysm

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      Authors: Daniel J. Tyrrell Judy Chen Benjamin Y. Li Sherri C. Wood Wendy Rosebury-Smith Henriette A. Remmer Longtan Jiang Min Zhang Morgan Salmon Gorav Ailawadi Bo Yang Daniel R. Goldstein Department of Internal Medicine; University of Michigan, Ann Arbor. (D.J.T., J.C., B.Y.L., S.C.W., D.R.G.) Program on Immunology, University of Michigan, Ann Arbor. (J.C., D.R.G.) Unit for Laboratory Animal Management, University of Michigan, Ann Arbor. (W.R.-S.) Proteomics & Peptide Synthesis Core, University of Michigan, Ann Arbor. (H.A.R.) Department of Cardiac Surgery, University of Michigan, Ann Arbor. (L.J., M.S., G.A., B.Y.) Department of Biostatistics, University of Michigan, Ann Arbor. (M.Z.) Department of Microbiology Immunology, University of Michigan, Ann Arbor. (D.R.G.)
      First page: 1060
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Aging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear.Methods:We employed a human aortic biorepository of healthy specimens (n=17) and those that underwent surgical repair for TAA (n=20). First, we performed proteomics comparing aortas of healthy donors to aneurysmal specimens, in young (ie, <60 years of age) and old (ie, ≥60 years of age) subjects. Second, we measured proteins, via immunoblotting, involved in mitophagy (ie, Parkin) and also mitochondrial-induced inflammatory pathways, specifically TLR (toll-like receptor) 9, STING (stimulator of interferon genes), and IFN (interferon)-β.Results:Proteomics revealed that aging transformed the aorta both quantitatively and qualitatively from health to TAA. Whereas young aortas exhibited an enrichment of immunologic processes, older aortas exhibited an enrichment of metabolic processes. Immunoblotting revealed that the expression of Parkin directly correlated to subject age in health but inversely to subject age in TAA. In TAA, but not in health, phosphorylation of STING and the expression of IFN-β was impacted by aging regardless of whether subjects had bicuspid or tricuspid valves. In subjects with bicuspid valves and TAAs, TLR9 expression positively correlated with subject age. Interestingly, whereas phosphorylation of STING was inversely correlated with subject age, IFN-β positively correlated with subject age.Conclusions:Aging transforms the human aortic proteome from health to TAA, leading to a differential regulation of biological processes. Our results suggest that the development of therapies to mitigate vascular diseases including TAA may need to be modified depending on subject age.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-05-05T09:00:02Z
      DOI: 10.1161/ATVBAHA.122.317643
       
  • Vascular Aging and Vascular Disease Have Much in Common!

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      Authors: Anna M.D. Watson Yung-Chih Chen Karlheinz Peter Atherothrombosis; Diabetes Institute, Central Clinical School, Monash University, Melbourne, VIC, Australia. Department of Cardiometabolic Health, University of Melbourne, VIC, Australia.
      First page: 1077
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.

      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-23T09:00:03Z
      DOI: 10.1161/ATVBAHA.122.317892
       
  • Gut Microbiota, Plasma Metabolomic Profiles, and Carotid Artery
           Atherosclerosis in HIV Infection

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      Authors: Zheng Wang Brandilyn A. Peters Mykhaylo Usyk Jiaqian Xing David B. Hanna Tao Wang Wendy S. Post Alan L. Landay Howard N. Hodis Kathleen Weber Audrey French Elizabeth T. Golub Jason Lazar Deborah Gustafson Seble Kassaye Bradley Aouizerat Sabina Haberlen Carlos Malvestutto Matthew Budoff Steven M. Wolinsky Anjali Sharma Kathryn Anastos Clary B. Clish Robert C. Kaplan Robert D. Burk Qibin Qi Department of Epidemiology; Harvard, Cambridge, MA (C.B.C.). Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (R.C.K.). Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (Q.Q.).
      First page: 1081
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection.Methods:We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up.Results:We found 2 potentially pathogenic bacteria,FusobacteriumandProteus, were associated with carotid artery plaque; while the beneficial butyrate producerOdoribacterwas inversely associated with plaque.FusobacteriumandProteuswere associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09–1.64] and 1.24 [1.02–1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines.Conclusions:Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-09T09:00:15Z
      DOI: 10.1161/ATVBAHA.121.317276
       
  • Carotid Siphon Calcification Predicts the Symptomatic Progression in
           Branch Artery Disease With Intracranial Artery Stenosis

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      Authors: Duanlu Hou Xiaoli Yang Yuanyuan Wang Shengwen Huang Yuping Tang Danhong Wu Department of Neurology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China. (D.H; X.Y, Y.W, S.H, D.W.) Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China. (Y.T.)
      First page: 1094
      Abstract: Arteriosclerosis, Thrombosis, and Vascular Biology, Ahead of Print.
      Background:Arterial calcification in the aortic arch, carotid bifurcation, or siphon on computed tomography was associated with cardiovascular disease. The association between arterial calcification prevalence and progression of branch atheromatous disease (BAD) in intracranial artery atherosclerosis was little investigated.Methods:This study included 310 patients with ischemic stroke from one stroke center. Patients were divided into BAD (110) and non-BAD groups (200). Baseline characteristics, lipids, and arterial calcification were measured. The primary outcome was the prevalence of arterial calcification in BAD progression, and the secondary outcome was the prevalence of calcification in arterial stenosis. The association or correlation among calcification prevalence, lipid markers, and BAD progression was analyzed using logistic regression, receiver operating characteristic curve, and linear regression.Results:Our study found that carotid siphon calcification on computed angiography was more prevalent (P=0.01) in patients with BAD and also more prevalent (P<0.001) in intracranial artery stenosis, and its computed tomography values could independently predict the symptomatic progression (P=0.01). Furthermore, a strong linear correlation between oxidized lipid and calcification density was found (beta=−0.73,P=0.0048) in patients with BAD, a subtype (B-type) of intracranial arterial atherosclerotic disease.Conclusions:We found that carotid siphon calcification was associated with BAD and its computed tomography values could predict the symptomatic progression in patients with intracranial arterial atherosclerotic disease and BAD, indicating the important role of carotid calcification in B-type intracranial arterial atherosclerotic disease.REGISTRATION:URL:http://www.chictr.org.cn; Unique identifier: ChiCTR1800018315
      Citation: Arteriosclerosis, Thrombosis, and Vascular Biology
      PubDate: 2022-06-02T09:00:07Z
      DOI: 10.1161/ATVBAHA.122.317670
       
 
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