Subjects -> MEDICAL SCIENCES (Total: 8359 journals)
    - ANAESTHESIOLOGY (119 journals)
    - CARDIOVASCULAR DISEASES (329 journals)
    - DENTISTRY (288 journals)
    - ENDOCRINOLOGY (148 journals)
    - FORENSIC SCIENCES (41 journals)
    - HEMATOLOGY (153 journals)
    - HYPNOSIS (4 journals)
    - INTERNAL MEDICINE (164 journals)
    - MEDICAL GENETICS (58 journals)
    - MEDICAL SCIENCES (2268 journals)
    - NURSES AND NURSING (356 journals)
    - OBSTETRICS AND GYNECOLOGY (202 journals)
    - ONCOLOGY (377 journals)
    - OTORHINOLARYNGOLOGY (80 journals)
    - PATHOLOGY (96 journals)
    - PEDIATRICS (270 journals)
    - PSYCHIATRY AND NEUROLOGY (813 journals)
    - RESPIRATORY DISEASES (102 journals)
    - RHEUMATOLOGY (76 journals)
    - SPORTS MEDICINE (78 journals)
    - SURGERY (393 journals)

CARDIOVASCULAR DISEASES (329 journals)                  1 2 | Last

Showing 1 - 200 of 329 Journals sorted alphabetically
Acta Angiologica     Open Access   (Followers: 5)
Acta Cardiologica     Hybrid Journal   (Followers: 2)
Acute Cardiac Care     Hybrid Journal   (Followers: 7)
Adipositas - Ursachen, Folgeerkrankungen, Therapie     Hybrid Journal  
AJP Heart and Circulatory Physiology     Hybrid Journal   (Followers: 12)
Aktuelle Kardiologie     Hybrid Journal   (Followers: 1)
American Heart Journal     Hybrid Journal   (Followers: 58)
American Journal of Cardiology     Hybrid Journal   (Followers: 67)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 17)
American Journal of Hypertension     Hybrid Journal   (Followers: 28)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anatolian Journal of Cardiology     Open Access   (Followers: 6)
Angiología     Full-text available via subscription  
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)
Angiology     Hybrid Journal   (Followers: 3)
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (Followers: 1)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1)
Annals of Pediatric Cardiology     Open Access   (Followers: 12)
AORTA     Open Access  
Archives of Cardiovascular Diseases     Full-text available via subscription   (Followers: 5)
Archives of Cardiovascular Diseases Supplements     Full-text available via subscription   (Followers: 3)
Archives of Cardiovascular Imaging     Open Access   (Followers: 2)
Archivos de cardiología de México     Open Access   (Followers: 1)
Argentine Journal of Cardiology (English edition)     Open Access   (Followers: 2)
Arquivos Brasileiros de Cardiologia     Open Access   (Followers: 1)
Arteriosclerosis, Thrombosis and Vascular Biology     Full-text available via subscription   (Followers: 32)
Artery Research     Hybrid Journal   (Followers: 4)
ARYA Atherosclerosis     Open Access  
ASAIO Journal     Hybrid Journal   (Followers: 3)
ASEAN Heart Journal     Open Access   (Followers: 2)
Asian Cardiovascular and Thoracic Annals     Hybrid Journal   (Followers: 2)
Aswan Heart Centre Science & Practice Services     Open Access   (Followers: 1)
Atherosclerosis : X     Open Access  
Bangladesh Heart Journal     Open Access   (Followers: 3)
Basic Research in Cardiology     Hybrid Journal   (Followers: 10)
BMC Cardiovascular Disorders     Open Access   (Followers: 22)
Brain Circulation     Open Access   (Followers: 1)
British Journal of Cardiology     Full-text available via subscription   (Followers: 16)
Canadian Journal of Cardiology     Hybrid Journal   (Followers: 18)
Cardiac Cath Lab Director     Full-text available via subscription  
Cardiac Electrophysiology Review     Hybrid Journal   (Followers: 2)
Cardiocore     Full-text available via subscription   (Followers: 1)
Cardiogenetics     Open Access   (Followers: 3)
Cardiology     Full-text available via subscription   (Followers: 20)
Cardiology and Angiology: An International Journal     Open Access  
Cardiology and Therapy     Open Access   (Followers: 12)
Cardiology Clinics     Full-text available via subscription   (Followers: 14)
Cardiology in Review     Hybrid Journal   (Followers: 8)
Cardiology in the Young     Hybrid Journal   (Followers: 34)
Cardiology Journal     Open Access   (Followers: 6)
Cardiology Plus     Open Access   (Followers: 1)
Cardiology Research     Open Access   (Followers: 15)
Cardiology Research and Practice     Open Access   (Followers: 10)
Cardiopulmonary Physical Therapy Journal     Hybrid Journal   (Followers: 7)
Cardiorenal Medicine     Full-text available via subscription   (Followers: 1)
Cardiothoracic Surgeon     Open Access  
CardioVasc     Full-text available via subscription   (Followers: 1)
Cardiovascular & Haematological Disorders - Drug Targets     Hybrid Journal   (Followers: 1)
Cardiovascular & Hematological Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 2)
CardioVascular and Interventional Radiology     Hybrid Journal   (Followers: 15)
Cardiovascular and Thoracic Open     Open Access  
Cardiovascular Diabetology     Open Access   (Followers: 10)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 14)
Cardiovascular Endocrinology & Metabolism     Hybrid Journal   (Followers: 1)
Cardiovascular Engineering     Hybrid Journal   (Followers: 1)
Cardiovascular Engineering and Technology     Hybrid Journal   (Followers: 1)
Cardiovascular Intervention and Therapeutics     Hybrid Journal   (Followers: 5)
Cardiovascular Journal     Open Access   (Followers: 6)
Cardiovascular Journal of Africa     Full-text available via subscription   (Followers: 5)
Cardiovascular Journal of South Africa     Full-text available via subscription   (Followers: 1)
Cardiovascular Medicine in General Practice     Full-text available via subscription   (Followers: 7)
Cardiovascular Pathology     Hybrid Journal   (Followers: 4)
Cardiovascular Regenerative Medicine     Open Access  
Cardiovascular Research     Hybrid Journal   (Followers: 15)
Cardiovascular Revascularization Medicine     Hybrid Journal   (Followers: 1)
Cardiovascular System     Open Access  
Cardiovascular Therapeutics     Open Access   (Followers: 1)
Cardiovascular Toxicology     Hybrid Journal   (Followers: 6)
Cardiovascular Ultrasound     Open Access   (Followers: 5)
Case Reports in Cardiology     Open Access   (Followers: 7)
Catheterization and Cardiovascular Interventions     Hybrid Journal   (Followers: 3)
Cerebrovascular Diseases     Full-text available via subscription   (Followers: 3)
Cerebrovascular Diseases Extra     Open Access  
Chest     Full-text available via subscription   (Followers: 100)
Choroby Serca i Naczyń     Open Access   (Followers: 1)
Circulation     Hybrid Journal   (Followers: 247)
Circulation : Cardiovascular Imaging     Hybrid Journal   (Followers: 15)
Circulation : Cardiovascular Interventions     Hybrid Journal   (Followers: 17)
Circulation : Cardiovascular Quality and Outcomes     Hybrid Journal   (Followers: 11)
Circulation : Genomic and Precision Medicine     Hybrid Journal   (Followers: 15)
Circulation : Heart Failure     Hybrid Journal   (Followers: 26)
Circulation Research     Hybrid Journal   (Followers: 36)
Cirugía Cardiovascular     Open Access  
Clínica e Investigación en Arteriosclerosis     Full-text available via subscription  
Clínica e Investigación en arteriosclerosis (English Edition)     Hybrid Journal  
Clinical and Experimental Hypertension     Hybrid Journal   (Followers: 3)
Clinical Cardiology     Hybrid Journal   (Followers: 11)
Clinical Hypertension     Open Access   (Followers: 5)
Clinical Medicine Insights : Cardiology     Open Access   (Followers: 6)
Clinical Research in Cardiology     Hybrid Journal   (Followers: 6)
Clinical Research in Cardiology Supplements     Hybrid Journal  
Clinical Trials and Regulatory Science in Cardiology     Open Access   (Followers: 4)
Congenital Heart Disease     Hybrid Journal   (Followers: 6)
Congestive Heart Failure     Hybrid Journal   (Followers: 4)
Cor et Vasa     Full-text available via subscription   (Followers: 1)
Coronary Artery Disease     Hybrid Journal   (Followers: 2)
CorSalud     Open Access  
Critical Pathways in Cardiology     Hybrid Journal   (Followers: 4)
Current Cardiology Reports     Hybrid Journal   (Followers: 7)
Current Cardiology Reviews     Hybrid Journal   (Followers: 4)
Current Cardiovascular Imaging Reports     Hybrid Journal   (Followers: 1)
Current Cardiovascular Risk Reports     Hybrid Journal  
Current Heart Failure Reports     Hybrid Journal   (Followers: 5)
Current Hypertension Reports     Hybrid Journal   (Followers: 6)
Current Hypertension Reviews     Hybrid Journal   (Followers: 6)
Current Opinion in Cardiology     Hybrid Journal   (Followers: 14)
Current Problems in Cardiology     Hybrid Journal   (Followers: 3)
Current Research : Cardiology     Full-text available via subscription   (Followers: 1)
Current Treatment Options in Cardiovascular Medicine     Hybrid Journal   (Followers: 1)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 5)
CVIR Endovascular     Open Access   (Followers: 1)
Der Kardiologe     Hybrid Journal   (Followers: 2)
Echo Research and Practice     Open Access   (Followers: 2)
Echocardiography     Hybrid Journal   (Followers: 4)
Egyptian Heart Journal     Open Access   (Followers: 2)
Egyptian Journal of Cardiothoracic Anesthesia     Open Access  
ESC Heart Failure     Open Access   (Followers: 4)
European Heart Journal     Hybrid Journal   (Followers: 67)
European Heart Journal - Cardiovascular Imaging     Hybrid Journal   (Followers: 10)
European Heart Journal - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 3)
European Heart Journal - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart Journal : Acute Cardiovascular Care     Hybrid Journal   (Followers: 1)
European Heart Journal : Case Reports     Open Access   (Followers: 1)
European Heart Journal Supplements     Hybrid Journal   (Followers: 8)
European Journal of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 9)
European Journal of Cardio-Thoracic Surgery Supplements     Full-text available via subscription   (Followers: 2)
European Journal of Cardiovascular Nursing     Hybrid Journal   (Followers: 5)
European Journal of Heart Failure     Hybrid Journal   (Followers: 14)
European Journal of Preventive Cardiology.     Hybrid Journal   (Followers: 6)
European Stroke Organisation     Hybrid Journal   (Followers: 3)
Experimental & Translational Stroke Medicine     Open Access   (Followers: 8)
Expert Review of Cardiovascular Therapy     Full-text available via subscription   (Followers: 3)
Folia Cardiologica     Open Access  
Forum Zaburzeń Metabolicznych     Hybrid Journal  
Frontiers in Cardiovascular Medicine     Open Access   (Followers: 1)
Future Cardiology     Hybrid Journal   (Followers: 6)
General Thoracic and Cardiovascular Surgery     Hybrid Journal   (Followers: 3)
Global Cardiology Science and Practice     Open Access   (Followers: 5)
Global Heart     Hybrid Journal   (Followers: 3)
Heart     Hybrid Journal   (Followers: 48)
Heart and Mind     Open Access  
Heart and Vessels     Hybrid Journal  
Heart Failure Clinics     Full-text available via subscription   (Followers: 2)
Heart Failure Reviews     Hybrid Journal   (Followers: 3)
Heart India     Open Access   (Followers: 2)
Heart International     Full-text available via subscription  
Heart Rhythm     Hybrid Journal   (Followers: 11)
Heart Views     Open Access   (Followers: 2)
HeartRhythm Case Reports     Open Access  
Hellenic Journal of Cardiology     Open Access   (Followers: 1)
Herz     Hybrid Journal   (Followers: 3)
High Blood Pressure & Cardiovascular Prevention     Full-text available via subscription   (Followers: 2)
Hypertension     Full-text available via subscription   (Followers: 23)
Hypertension in Pregnancy     Hybrid Journal   (Followers: 9)
Hypertension Research     Hybrid Journal   (Followers: 5)
Ibrahim Cardiac Medical Journal     Open Access  
IJC Heart & Vessels     Open Access   (Followers: 1)
IJC Heart & Vasculature     Open Access   (Followers: 1)
IJC Metabolic & Endocrine     Open Access   (Followers: 1)
Indian Heart Journal     Open Access   (Followers: 5)
Indian Journal of Cardiovascular Disease in Women WINCARS     Open Access  
Indian Journal of Thoracic and Cardiovascular Surgery     Hybrid Journal  
Indian Pacing and Electrophysiology Journal     Open Access   (Followers: 1)
Innovations : Technology and Techniques in Cardiothoracic and Vascular Surgery     Hybrid Journal   (Followers: 1)
Insuficiencia Cardíaca     Open Access  
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 7)
International Cardiovascular Forum Journal     Open Access  
International Journal of Angiology     Hybrid Journal   (Followers: 2)
International Journal of Cardiology     Hybrid Journal   (Followers: 18)
International Journal of Cardiovascular and Cerebrovascular Disease     Open Access   (Followers: 2)
International Journal of Cardiovascular Imaging     Hybrid Journal   (Followers: 2)
International Journal of Cardiovascular Research     Hybrid Journal   (Followers: 6)
International Journal of Heart Rhythm     Open Access  
International Journal of Hypertension     Open Access   (Followers: 8)
International Journal of Hyperthermia     Open Access  
International Journal of Stroke     Hybrid Journal   (Followers: 30)
International Journal of the Cardiovascular Academy     Open Access  
Interventional Cardiology Clinics     Full-text available via subscription   (Followers: 2)
Interventional Cardiology Review     Full-text available via subscription  
JACC : Basic to Translational Science     Open Access   (Followers: 5)
JACC : Cardiovascular Imaging     Hybrid Journal   (Followers: 18)
JACC : Cardiovascular Interventions     Hybrid Journal   (Followers: 17)
JACC : Heart Failure     Full-text available via subscription   (Followers: 14)
JAMA Cardiology     Hybrid Journal   (Followers: 28)
JMIR Cardio     Open Access  
Jornal Vascular Brasileiro     Open Access  
Journal of Clinical & Experimental Cardiology     Open Access   (Followers: 5)
Journal of Arrhythmia     Open Access  
Journal of Cardiac Critical Care TSS     Open Access   (Followers: 1)
Journal of Cardiac Failure     Hybrid Journal   (Followers: 1)

        1 2 | Last

Similar Journals
Journal Cover
Cardiovascular Research
Journal Prestige (SJR): 3.002
Citation Impact (citeScore): 5
Number of Followers: 15  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0008-6363 - ISSN (Online) 1755-3245
Published by Oxford University Press Homepage  [409 journals]
  • The DAPA-HF trial marks the beginning of a new era in the treatment of
           heart failure with reduced ejection fraction
    • Authors: Verma S.
      Abstract: SGLT2 inhibitorHeart failureReduced ejection fraction
      PubDate: Wed, 18 Dec 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz328
      Issue No: Vol. 116, No. 1 (2019)
  • Is the glass half full or half empty after PARAGON-HF'
    • Authors: Cohen-Solal A; Logeart D.
      Abstract: HFpEFSacubitril/valsartanPARAGONHeart failure
      PubDate: Wed, 18 Dec 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz326
      Issue No: Vol. 116, No. 1 (2019)
  • Highlights of AHA Scientific Sessions 2019: novel approaches in
           cardiovascular risk reduction
    • Authors: Akoumianakis I.
      Abstract: American Heart AssociationCardiologyClinical trialsCardiovascular medicineCardiovascular research
      PubDate: Wed, 18 Dec 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz319
      Issue No: Vol. 116, No. 1 (2019)
  • ‘Veni, Vidi, Vici’: how to arm your troops in the battlefield
           of cardiac repair
    • Authors: Bollini S.
      Abstract: ExosomesCardiac repairFibrosisCAR-T cellActivate myofibroblast
      PubDate: Wed, 18 Dec 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz325
      Issue No: Vol. 116, No. 1 (2019)
  • Scientists on the Spot: The complex inheritance of cardiac disorders
    • Authors: Patel J; Bezzina C.
      Abstract: Inherited cardiac arrhythmia syndromesSudden cardiac deathGenome-wide association studyPolygenic risk score
      PubDate: Wed, 18 Dec 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz295
      Issue No: Vol. 116, No. 1 (2019)
  • Scientific highlights from the Great Wall International Congress of
           Cardiology 2019
    • Authors: Du J; Zhang J.
      Abstract: ChinaCongressConferenceCardiology
      PubDate: Mon, 16 Dec 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz324
      Issue No: Vol. 116, No. 1 (2019)
  • Cardiovascular research highlights from the UK Biobank: opportunities and
    • Authors: Raisi-Estabragh Z; Petersen S.
      Abstract: UK BiobankBig dataEpidemiologyCardiovascular disease
      PubDate: Thu, 28 Nov 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz294
      Issue No: Vol. 116, No. 1 (2019)
  • New insight sheds light as to how nitrite might reduce blood pressure
           height: is this alright'
    • Authors: Van Beusecum J; Harrison D.
      Pages: 1 - 3
      Abstract: This editorial refers to ‘Long-lasting blood pressure lowering effects of nitrite are NO-independent and mediated by hydrogen peroxide, persulfides, and oxidation of protein kinase G1α redox signalling’, by M. Feelisch et al., pp. 51–62.
      PubDate: Wed, 09 Oct 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz248
      Issue No: Vol. 116, No. 1 (2019)
  • Multi-omics applied to fibromuscular dysplasia: first steps on a new
           research avenue
    • Authors: Bruno R; Mischak H, Persu A.
      Pages: 4 - 5
      Abstract: This editorial refers to ‘A plasma proteogenomic signature for fibromuscular dysplasia’, by J.W. Olin et al., pp. 63–77.
      PubDate: Mon, 11 Nov 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz307
      Issue No: Vol. 116, No. 1 (2019)
  • The enigma of anti-inflammatory therapy for the management of heart
    • Authors: Sack M.
      Pages: 6 - 8
      Abstract: This editorial refers to ‘High sensitivity C-reactive protein in chronic heart failure: patient characteristics, phenotypes and mode of death’, by P. Pellicori et al., pp. 91–100.
      PubDate: Wed, 30 Oct 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz270
      Issue No: Vol. 116, No. 1 (2019)
  • Minding the gaps in post-myocardial infarction mortality between Sweden
           and the UK
    • Authors: Peterson B; Bhatt D.
      Pages: 9 - 11
      Abstract: This editorial refers to ‘Statistics on mortality following acute myocardial infarction in 842897 Europeans’, by O.A. Alabas et al., pp. 149–157.
      PubDate: Thu, 28 Nov 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz281
      Issue No: Vol. 116, No. 1 (2019)
  • Palliative care for people living with heart failure: European Association
           for Palliative Care Task Force expert position statement
    • Authors: Sobanski P; Alt-Epping B, Currow D, et al.
      Pages: 12 - 27
      Abstract: AbstractContrary to common perception, modern palliative care (PC) is applicable to all people with an incurable disease, not only cancer. PC is appropriate at every stage of disease progression, when PC needs emerge. These needs can be of physical, emotional, social, or spiritual nature. This document encourages the use of validated assessment tools to recognize such needs and ascertain efficacy of management. PC interventions should be provided alongside cardiologic management. Treating breathlessness is more effective, when cardiologic management is supported by PC interventions. Treating other symptoms like pain or depression requires predominantly PC interventions. Advance Care Planning aims to ensure that the future treatment and care the person receives is concordant with their personal values and goals, even after losing decision-making capacity. It should include also disease specific aspects, such as modification of implantable device activity at the end of life. The Whole Person Care concept describes the inseparability of the physical, emotional, and spiritual dimensions of the human being. Addressing psychological and spiritual needs, together with medical treatment, maintains personal integrity and promotes emotional healing. Most PC concerns can be addressed by the usual care team, supported by a PC specialist if needed. During dying, the persons’ needs may change dynamically and intensive PC is often required. Following the death of a person, bereavement services benefit loved ones. The authors conclude that the inclusion of PC within the regular clinical framework for people with heart failure results in a substantial improvement in quality of life as well as comfort and dignity whilst dying.
      PubDate: Thu, 29 Aug 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz200
      Issue No: Vol. 116, No. 1 (2019)
  • Periodontitis is associated with hypertension: a systematic review and
    • Authors: Muñoz Aguilera E; Suvan J, Buti J, et al.
      Pages: 28 - 39
      Abstract: AbstractRecent evidence suggests a link between periodontitis (PD) and hypertension, but the nature of this association remains unclear. The overall aim of this review was to critically appraise the evidence linking these two common disorders. Systematic search was conducted for studies published up to December 2018. Prevalence of hypertension in patients with PD (moderate/severe groups) vs. those without PD (non-PD) was the primary outcome. Additional outcomes included adjusted mean difference in systolic (SBP) and diastolic (DBP) blood pressure (BP) levels in PD vs. non-PD, assessment of biomarkers in PD and hypertension, and BP changes after periodontal therapy. From 81 studies selected, 40 were included in quantitative meta-analyses. Diagnoses of moderate-severe PD [odds ratio (OR) = 1.22; 95% confidence interval (CI): 1.10–1.35] and severe PD (OR = 1.49; 95% CI: 1.09–2.05) were associated with hypertension. Prospective studies confirmed PD diagnosis increased likelihood of hypertension occurrence (OR = 1.68; 95% CI: 0.85–3.35). Patients with PD exhibited higher mean SBP [weighted mean difference (WMD) of 4.49 mmHg; 95% CI: 2.88–6.11] and DBP (2.03 mmHg; 95% CI: 1.25–2.81) when compared with non-PD. Lastly, only 5 out of 12 interventional studies confirmed a reduction in BP following periodontal therapy, ranging from 3 to 12.5 mmHg of SBP and from 0 to 10 mmHg of DBP. PD is associated with increased odds of hypertension (SORT C) and higher SBP/DBP levels. The evidence suggesting that PD therapy could reduce BP is inconclusive. Although additional research is warranted on this association, these results suggest that oral health assessment and management of PD could not only improve oral/overall health and quality of life but also be of relevance in the management of patients with hypertension.
      PubDate: Tue, 24 Sep 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz201
      Issue No: Vol. 116, No. 1 (2019)
  • Cardiovascular risk of electronic cigarettes: a review of preclinical and
           clinical studies
    • Authors: Buchanan N; Grimmer J, Tanwar V, et al.
      Pages: 40 - 50
      Abstract: AbstractCigarette smoking is the most preventable risk factor related to cardiovascular morbidity and mortality. Tobacco usage has declined in recent years; however, the use of alternative nicotine delivery methods, particularly e-cigarettes, has increased exponentially despite limited data on their short- and long-term safety and efficacy. Due to their unique properties, the impact of e-cigarettes on cardiovascular physiology is not fully known. Here, we summarize both preclinical and clinical data extracted from short- and long-term studies on the cardiovascular effects of e-cigarette use. Current findings support that e-cigarettes are not a harm-free alternative to tobacco smoke. However, the data are primarily derived from acute studies. The impact of chronic e-cigarette exposure is essentially unstudied. To explore the uniqueness of e-cigarettes, we contemplate the cardiovascular effects of individual e-cigarette constituents. Overall, data suggest that exposure to e-cigarettes could be a potential cardiovascular health concern. Further preclinical research and randomized trials are needed to expand basic and clinical investigations before considering e-cigarettes safe alternatives to conventional cigarettes.
      PubDate: Thu, 07 Nov 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz256
      Issue No: Vol. 116, No. 1 (2019)
  • Long-lasting blood pressure lowering effects of nitrite are NO-independent
           and mediated by hydrogen peroxide, persulfides, and oxidation of protein
           kinase G1α redox signalling
    • Authors: Feelisch M; Akaike T, Griffiths K, et al.
      Pages: 51 - 62
      Abstract: AbstractAimsUnder hypoxic conditions, nitrite (NO2−) can be reduced to nitric oxide (NO) eliciting vasorelaxation. However, nitrite also exerts vasorelaxant effects of potential therapeutic relevance under normal physiological conditions via undetermined mechanisms. We, therefore, sought to investigate the mechanism(s) by which nitrite regulates the vascular system in normoxia and, specifically, whether the biological effects are a result of NO generation (as in hypoxia) or mediated via alternative mechanisms involving classical downstream targets of NO [e.g. effects on protein kinase G1α (PKG1α)].Methods and resultsEx vivo myography revealed that, unlike in thoracic aorta (conduit vessels), the vasorelaxant effects of nitrite in mesenteric resistance vessels from wild-type (WT) mice were NO-independent. Oxidants such as H2O2 promote disulfide formation of PKG1α, resulting in NO- cyclic guanosine monophosphate (cGMP) independent kinase activation. To explore whether the microvascular effects of nitrite were associated with PKG1α oxidation, we used a Cys42Ser PKG1α knock-in (C42S PKG1α KI; ‘redox-dead’) mouse that cannot transduce oxidant signals. Resistance vessels from these C42S PKG1α KI mice were markedly less responsive to nitrite-induced vasodilation. Intraperitoneal (i.p.) bolus application of nitrite in conscious WT mice induced a rapid yet transient increase in plasma nitrite and cGMP concentrations followed by prolonged hypotensive effects, as assessed using in vivo telemetry. In the C42S PKG1α KI mice, the blood pressure lowering effects of nitrite were lower compared to WT. Increased H2O2 concentrations were detected in WT resistance vessel tissue challenged with nitrite. Consistent with this, increased cysteine and glutathione persulfide levels were detected in these vessels by mass spectrometry, matching the temporal profile of nitrite’s effects on H2O2 and blood pressure.ConclusionUnder physiological conditions, nitrite induces a delayed and long-lasting blood pressure lowering effect, which is NO-independent and occurs via a new redox mechanism involving H2O2, persulfides, and PKG1α oxidation/activation. Targeting this novel pathway may provide new prospects for anti-hypertensive therapy.
      PubDate: Thu, 01 Aug 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz202
      Issue No: Vol. 116, No. 1 (2019)
  • A plasma proteogenomic signature for fibromuscular dysplasia
    • Authors: Olin J; Di Narzo A, d’Escamard V, et al.
      Pages: 63 - 77
      Abstract: AbstractAimsFibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test.Methods and resultsFemales with ‘multifocal’ FMD and matched healthy controls underwent clinical phenotyping, dermal biopsy, and blood draw. Using dual-capture proximity extension assay and nuclear magnetic resonance-spectroscopy, we evaluated plasma levels of 981 proteins and 31 lipid sub-classes, respectively. In a discovery cohort (Ncases = 90, Ncontrols = 100), we identified 105 proteins and 16 lipid sub-classes (predominantly triglycerides and fatty acids) with differential plasma abundance in FMD cases vs. controls. In an independent cohort (Ncases = 23, Ncontrols = 28), we successfully validated 37 plasma proteins and 10 lipid sub-classes with differential abundance. Among these, 5/37 proteins exhibited genetic control and Bayesian analyses identified 3 of these as potential upstream drivers of FMD. In a 3rd cohort (Ncases = 506, Ncontrols = 876) the genetic locus of one of these upstream disease drivers, CD2-associated protein (CD2AP), was independently validated as being associated with risk of having FMD (odds ratios  = 1.36; P = 0.0003). Immune-fluorescence staining identified that CD2AP is expressed by the endothelium of medium-large arteries. Finally, machine learning trained on the discovery cohort was used to develop a test for FMD. When independently applied to the validation cohort, the test showed a c-statistic of 0.73 and sensitivity of 78.3%.ConclusionFMD exhibits a plasma proteogenomic and lipid signature that includes potential causative disease drivers, and which holds promise for developing a blood-based test for this disease.
      PubDate: Mon, 19 Aug 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz219
      Issue No: Vol. 116, No. 1 (2019)
  • Coupling of the Na+/K+-ATPase to Ankyrin B controls Na+/Ca2+ exchanger
           activity in cardiomyocytes
    • Authors: Skogestad J; Aronsen J, Tovsrud N, et al.
      Pages: 78 - 90
      Abstract: AbstractAimsAnkyrin B (AnkB) is an adaptor protein that assembles Na+/K+-ATPase (NKA) and Na+/Ca2+ exchanger (NCX) in the AnkB macromolecular complex. Loss-of-function mutations in AnkB cause the AnkB syndrome in humans, characterized by ventricular arrhythmias and sudden cardiac death. It is unclear to what extent NKA binding to AnkB allows regulation of local Na+ and Ca2+ domains and hence NCX activity.Methods and resultsTo investigate the role of NKA binding to AnkB in cardiomyocytes, we synthesized a disruptor peptide (MAB peptide) and its AnkB binding ability was verified by pulldown experiments. As opposed to control, the correlation between NKA and NCX currents was abolished in adult rat ventricular myocytes dialyzed with MAB peptide, as well as in cardiomyocytes from AnkB+/− mice. Disruption of NKA from AnkB (with MAB peptide) increased NCX-sensed cytosolic Na+ concentration, reduced Ca2+ extrusion through NCX, and increased frequency of Ca2+ sparks and Ca2+ waves without concomitant increase in Ca2+ transient amplitude or SR Ca2+ load, suggesting an effect in local Ca2+ domains. Selective inhibition of the NKAα2 isoform abolished both the correlation between NKA and NCX currents and the increased rate of Ca2+ sparks and waves following NKA/AnkB disruption, suggesting that an AnkB/NKAα2/NCX domain controls Ca2+ fluxes in cardiomyocytes.ConclusionNKA binding to AnkB allows ion regulation in a local domain, and acute disruption of the NKA/AnkB interaction using disruptor peptides lead to increased rate of Ca2+ sparks and waves. The functional effects were mediated through the NKAα2 isoform. Disruption of the AnkB/NKA/NCX domain could be an important pathophysiological mechanism in the AnkB syndrome.
      PubDate: Fri, 05 Apr 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz087
      Issue No: Vol. 116, No. 1 (2019)
  • High-sensitivity C-reactive protein in chronic heart failure: patient
           characteristics, phenotypes, and mode of death
    • Authors: Pellicori P; Zhang J, Cuthbert J, et al.
      Pages: 91 - 100
      Abstract: AbstractAimsPlasma concentrations of high-sensitivity C-reactive protein (hsCRP) are often raised in chronic heart failure (CHF) and might indicate inflammatory processes that could be a therapeutic target. We aimed to study the associations between hsCRP, mode and cause of death in patients with CHF.Methods and resultsWe enrolled 4423 patients referred to a heart failure clinic serving a local population. CHF was defined as relevant symptoms or signs with either a reduced left ventricular ejection fraction <40% or raised plasma concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP >125 pg/mL). The median [interquartile range (IQR)] plasma hsCRP for patients diagnosed with CHF (n = 3756) was 3.9 (1.6–8.5) mg/L and 2.7 (1.3–5.1) mg/L for those who were not (n = 667; P < 0.001). Patients with hsCRP ≥10 mg/L (N = 809; 22%) were older and more congested than those with hsCRP <2 mg/L (N = 1117, 30%). During a median follow-up of 53 (IQR 28–93) months, 1784 (48%) patients with CHF died. Higher plasma hsCRP was associated with greater mortality, independent of age, symptom severity, creatinine, and NT-proBNP. Comparing a hsCRP ≥10 mg/L to <2 mg/L, the hazard ratio for all-cause mortality was 2.49 (95% confidence interval 2.19–2.84; P < 0.001), for cardiovascular (CV) mortality was 2.26 (1.91–2.68; P < 0.001), and for non-CV mortality was 2.96 (2.40–3.65; P < 0.001).ConclusionIn patients with CHF, a raised plasma hsCRP is associated with more congestion and a worse prognosis. The proportion of deaths that are non-CV also increases with higher hsCRP.
      PubDate: Fri, 26 Jul 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz198
      Issue No: Vol. 116, No. 1 (2019)
  • Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and
           heart failure in mice by blocking the activation of β-catenin
    • Authors: Lin H; Li Y, Zhu H, et al.
      Pages: 101 - 113
      Abstract: AbstractAimsProton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms.Methods and resultsAdult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy.ConclusionLansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.
      PubDate: Thu, 24 Jan 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz016
      Issue No: Vol. 116, No. 1 (2019)
  • Sialyltransferase7A promotes angiotensin II-induced cardiomyocyte
           hypertrophy via HIF-1α-TAK1 signalling pathway
    • Authors: Yan X; Zhao R, Feng X, et al.
      Pages: 114 - 126
      Abstract: AbstractAimsSialylation is up-regulated during the development of cardiac hypertrophy. Sialyltransferase7A (Siat7A) mRNA is consistently over-expressed in the hypertrophic left ventricle of hypertensive rats independently of genetic background. The aims of this study were: (i) to detect the Siat7A protein levels and its roles in the pathological cardiomyocyte hypertrophy; (ii) to elucidate the effect of sialylation mediated by Siat7A on the transforming-growth-factor-β-activated kinase (TAK1) expression and activity in cardiomyocyte hypertrophy; and (iii) to clarify hypoxia-inducible factor 1 (HIF-1) expression was regulated by Siat7A and transactivated TAK1 expression in cardiomyocyte hypertrophy.Methods and resultsSiat7A protein level was increased in hypertrophic cardiomyocytes of human and rats subjected to chronic infusion of angiotensin II (ANG II). Delivery of adeno-associated viral (AAV9) bearing shRNA against rat Siat7A into the left ventricular wall inhibited ventricular hypertrophy. Cardiac-specific Siat7A overexpression via intravenous injection of an AAV9 vector encoding Siat7A under the cardiac troponin T (cTNT) promoter aggravated cardiac hypertrophy in ANG II-treated rats. In vitro, Siat7A knockdown inhibited the induction of Sialyl-Tn (sTn) antigen and cardiomyocyte hypertrophy stimulated by ANG II. Mechanistically, ANG II induced the activation of TAK1-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling in parallel to up-regulation of Siat7A in hypertrophic cardiomyocytes. Siat7A knockdown inhibited activation of TAK1-NF-κB pathway. Interestingly, HIF-1α expression was increased in cardiomyocytes stimulated by ANG II but decreased after Siat7A knockdown. HIF-1α knockdown efficiently decreased TAK1 expression. ChIP and luciferase assays showed that HIF-1α transactivated the TAK1 promoter region (nt −1285 to −1274 bp) in the cardiomyocytes following ANG II stimulus.ConclusionSiat7A was up-regulated in hypertrophic myocardium and promoted cardiomyocyte hypertrophy via activation of the HIF-1α-TAK1-NF-κB pathway.
      PubDate: Mon, 11 Mar 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz064
      Issue No: Vol. 116, No. 1 (2019)
  • Stretching single titin molecules from failing human hearts reveals
           titin’s role in blunting cardiac kinetic reserve
    • Authors: Chen M; Kiduko S, Saad N, et al.
      Pages: 127 - 137
      Abstract: AbstractAimsHeart failure (HF) patients commonly experience symptoms primarily during elevated heart rates, as a result of physical activities or stress. A main determinant of diastolic passive tension, the elastic sarcomeric protein titin, has been shown to be associated with HF, with unresolved involvement regarding its role at different heart rates. To determine whether titin is playing a role in the heart rate (frequency-) dependent acceleration of relaxation (FDAR). W, we studied the FDAR responses in live human left ventricular cardiomyocytes and the corresponding titin-based passive tension (TPT) from failing and non-failing human hearts.Methods and resultsUsing atomic force, we developed a novel single-molecule force spectroscopy approach to detect TPT based on the frequency-modulated cardiac cycle. Mean TPT reduced upon an increased heart rate in non-failing human hearts, while this reduction was significantly blunted in failing human hearts. These mechanical changes in the titin distal Ig domain significantly correlated with the frequency-dependent relaxation kinetics of human cardiomyocytes obtained from the corresponding hearts. Furthermore, the data suggested that the higher the TPT, the faster the cardiomyocytes relaxed, but the lower the potential of myocytes to speed up relaxation at a higher heart rate. Such poorer FDAR response was also associated with a lesser reduction or a bigger increase in TPT upon elevated heart rate.ConclusionsOur study established a novel approach in detecting dynamic heart rate relevant tension changes physiologically on native titin domains. Using this approach, the data suggested that the regulation of kinetic reserve in cardiac relaxation and its pathological changes were associated with the intensity and dynamic changes of passive tension by titin.
      PubDate: Mon, 18 Feb 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz043
      Issue No: Vol. 116, No. 1 (2019)
  • Genome-wide association study identifies locus at chromosome 2q32.1
           associated with syncope and collapse
    • Authors: Hadji-Turdeghal K; Andreasen L, Hagen C, et al.
      Pages: 138 - 148
      Abstract: AbstractAimsSyncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse.Methods and resultsWe used genome-wide association data on syncope on 408 961 individuals with European ancestry from the UK Biobank study. In a replication study, we used the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), to investigate the risk of incident syncope stratified by genotype carrier status. We report on a genome-wide significant locus located on chromosome 2q32.1 [odds ratio = 1.13, 95% confidence interval (CI) 1.10–1.17, P = 5.8 × 10−15], with lead single nucleotide polymorphism rs12465214 in proximity to the gene zinc finger protein 804a (ZNF804A). This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (1.30, 95% CI 1.15–1.46, P = 1.68 × 10−5) of incident syncope. Quantitative polymerase chain reaction analysis showed ZNF804A to be expressed most abundantly in brain tissue.ConclusionWe identified a genome-wide significant locus (rs12465214) associated with syncope and collapse. The association was replicated in an independent cohort. This is the first genome-wide association study to associate a locus with syncope and collapse.
      PubDate: Fri, 03 May 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz106
      Issue No: Vol. 116, No. 1 (2019)
  • Statistics on mortality following acute myocardial infarction in
           842 897 Europeans
    • Authors: Alabas O; Jernberg T, Pujades-Rodriguez M, et al.
      Pages: 149 - 157
      Abstract: AbstractAimsTo compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments.Methods and resultsNational data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 patients, Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)] and the UK [n = 247, 662 529 patients, Myocardial Ischaemia National Audit Project (MINAP)] between 2003 and 2013. There were lower rates of revascularization [STEMI (43.8% vs. 74.9%); NSTEMI (27.5% vs. 43.6%)] and pharmacotherapies at time of hospital discharge including [aspirin (82.9% vs. 90.2%) and (79.9% vs. 88.0%), β-blockers (73.4% vs. 86.4%) and (65.3% vs. 85.1%)] in the UK compared with Sweden, respectively. Standardized net probability of death (NPD) between admission and 1 month was higher in the UK for STEMI [8.0 (95% confidence interval 7.4–8.5) vs. 6.7 (6.5–6.9)] and NSTEMI [6.8 (6.4–7.2) vs. 4.9 (4.7–5.0)]. Between 6 months and 1 year and more than 1 year, NPD remained higher in the UK for NSTEMI [2.9 (2.5–3.3) vs. 2.3 (2.2–2.5)] and [21.4 (20.0–22.8) vs. 18.3 (17.6–19.0)], but was similar for STEMI [0.7 (0.4–1.0) vs. 0.9 (0.7–1.0)] and [8.4 (6.7–10.1) vs. 8.3 (7.5–9.1)].ConclusionShort-term mortality following STEMI and NSTEMI was higher in the UK compared with Sweden. Mid- and longer-term mortality remained higher in the UK for NSTEMI but was similar for STEMI. Differences in mortality may be due to differential use of guideline-indicated treatments.
      PubDate: Fri, 26 Jul 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz197
      Issue No: Vol. 116, No. 1 (2019)
  • Carbon monoxide improves haemodynamics during extracorporeal resuscitation
           in pigs
    • Authors: Wollborn J; Steiger C, Ruetten E, et al.
      Pages: 158 - 170
      Abstract: AbstractAimsHeart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism.Methods and resultsIn an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P < 0.05). While sublingual microcirculation was significantly compromised in CPR and E-CPR, CO delivery demonstrated a significant improvement in microvascular function (microvascular flow index: Sham 2.9 ± 0.1; CPR 2.2 ± 0.1; E-CPR 1.8 ± 0.1; CO-E-CPR 2.7 ± 0.1; P < 0.01). Histological and serological myocardial damage markers were significantly reduced (hsTroponin-T Sham 0.01 ± 0.001; CPR 1.9 ± 0.2; E-CPR 3.5 ± 1.2; CO-E-CPR 0.5 ± 0.2 ng/mL; P < 0.05). DAMP signalling was decreased ipse facto leading to influence of cardioprotective heat shock and cyclooxygenase response.ConclusionsCO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs.
      PubDate: Thu, 14 Mar 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz075
      Issue No: Vol. 116, No. 1 (2019)
  • PBI-4050 reduces pulmonary hypertension, lung fibrosis, and right
           ventricular dysfunction in heart failure
    • Authors: Nguyen Q; Nsaibia M, Sirois M, et al.
      Pages: 171 - 182
      Abstract: AbstractAimsHeart failure with reduced ejection fraction (HFrEF) causes lung remodelling with myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome with pulmonary hypertension (PH) and right ventricular (RV) dysfunction. PBI-4050 is a first-in-class anti-fibrotic, anti-inflammatory, and anti-proliferative compound. The present study evaluated the therapeutic impact of PBI-4050 on PH in an HFrEF model.Methods and resultsHFrEF was induced after myocardial infarction (MI) in rats. Two weeks later, sham-operated and MI groups received PBI-4050 (200 mg/kg/day by gavage) or saline for 3 weeks. Animals were analysed according to infarct size as large (≥30% left ventricle) or medium MI (<30%). Large MI caused PH and RV hypertrophy (RVH) with a restrictive lung syndrome. PBI-4050 did not adversely affect left ventricular (LV) function but markedly reduced PH and RVH and improved RV dysfunction. PBI-4050 reduced lung remodelling and improved respiratory compliance with decreased lung fibrosis, alveolar wall cellular proliferation and α-smooth muscle actin expression. The increased expression of endothelin-1 (ET-1), transforming growth factor beta (TGF-β), interleukin-6 (IL-6) and of tissue inhibitor of metalloprotease-1 in the lungs from HFrEF were reduced with PBI-4050 therapy. Activation of isolated human lung fibroblasts (HLFs) to a myofibroblastic pro-fibrogenic phenotype was markedly reduced by PBI-4050. The fatty acid receptor GPR84 was increased in HFrEF lungs and in activated HLFs, and reduced by PBI-4050. GPR84 agonists activated fibrogenesis in HLFs and finally, PBI-4050 reduced ERK1/2 phosphorylation.ConclusionsPBI-4050 reduces PH and RVH in HFrEF by decreasing lung fibrosis and remodelling. This novel agent decreases the associated restrictive lung syndrome and recovers RV function. A contributing mechanism involves reducing the activation of lung fibroblasts by IL-6, TGF-β, and ET-1 by antagonism of GPR84 and reduced ERK1/2 phosphorylation. PBI-4050 is a novel promising therapy for targeting lung remodelling in group II PH.
      PubDate: Thu, 07 Feb 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz034
      Issue No: Vol. 116, No. 1 (2019)
  • Perinatal iron deficiency and a high salt diet cause long-term kidney
           mitochondrial dysfunction and oxidative stress
    • Authors: Woodman A; Mah R, Keddie D, et al.
      Pages: 183 - 192
      Abstract: AbstractAimsPerinatal iron deficiency (ID) alters developmental trajectories of offspring, predisposing them to cardiovascular dysfunction in later life. The mechanisms underlying this long-term programming of renal function have not been defined. We hypothesized perinatal ID causes hypertension and alters kidney metabolic function and morphology in a sex-dependent manner in adult offspring. Furthermore, we hypothesized these effects are exacerbated by chronic consumption of a high salt diet.Methods and resultsPregnant Sprague Dawley rats were fed either an iron-restricted or replete diet prior to and throughout pregnancy. Adult offspring were fed normal or high salt diets for 6 weeks prior to experimentation at 6 months of age. Blood pressure (BP) was assessed via indwelling catheters in anaesthetized offspring; kidney mitochondrial function was assessed via high-resolution respirometry; reactive oxygen species and nitric oxide were quantified via fluorescence microscopy. Adult males, but not females, exhibited increased systolic BP due to ID (P = 0.01) and high salt intake (P = 0.02). In males, but not in females, medullary mitochondrial content was increased by high salt (P = 0.003), while succinate-dependent respiration was reduced by ID (P < 0.05). The combination of perinatal ID and high salt reduced complex IV activity in the cortex of males (P = 0.01). Perinatal ID increased cytosolic superoxide generation (P < 0.001) concomitant with reduced nitric oxide bioavailability (P < 0.001) in male offspring, while high salt increased mitochondrial superoxide in the medulla (P = 0.04) and cytosolic superoxide within the cortex (P = 0.01). Male offspring exhibited glomerular basement membrane thickening (P < 0.05), increased collagen deposition (P < 0.05), and glomerular hypertrophy (interaction, P = 0.02) due to both perinatal ID and high salt. Female offspring exhibited no alterations in mitochondrial function or morphology due to either high salt or ID.ConclusionPerinatal ID causes long-term sex-dependent alterations in renal metabolic function and morphology, potentially contributing to hypertension and increased cardiovascular disease risk.
      PubDate: Thu, 31 Jan 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz029
      Issue No: Vol. 116, No. 1 (2019)
  • Epidermal growth factor-like repeats of SCUBE1 derived from platelets are
           critical for thrombus formation
    • Authors: Liao W; Wu M, Peng C, et al.
      Pages: 193 - 201
      Abstract: AbstractAimsSCUBE1 [signal peptide-CUB-epidermal growth factor (EGF) domain-containing protein 1], expressed in endothelial cells (ECs) and platelets, exists in soluble or membrane forms. We previously showed that soluble SCUBE1 is a biomarker for platelet activation and also an active participant of thrombosis. However, whether the adhesive module of its EGF-like repeats is essential and the specific contribution of SCUBE1 synthesized in ECs or platelets to thrombosis in vivo remain unclear.Methods and resultsWe generated new mutant (Δ2) mice lacking the entire EGF-like repeats to evaluate the module’s functional importance during thrombogenesis in vivo. The Δ2 platelet-rich plasma showed markedly impaired platelet aggregation induced by agonists including adenosine diphosphate, collagen, the thrombin agonist PAR-4 peptide and the thromboxane A2 analogue U46619. Consistently, genetic ablation of the EGF-like repeats diminished arterial thrombosis and protected Δ2 mice against lethal thromboembolism. On flow chamber assay, whole blood isolated from Δ2 or wild-type (WT) mice pre-treated with blocking antibodies against the EGF-like repeats showed a significant decrease in platelet deposition and thrombus formation on collagen-coated surfaces under arterial shear rates. Moreover, we created animals expressing SCUBE1 only in ECs (S1-EC) or platelets (S1-PLT) by reciprocal bone-marrow transplantation between WT and Δ2 mice. The time of carotid arterial thrombosis induced by ferric chloride was normal in S1-PLT chimeric mice but much prolonged in S1-EC animals.ConclusionsWe demonstrate that platelet-derived SCUBE1 plays a critical role in arterial thrombosis via its adhesive EGF-like repeats in vivo and suggest targeting these adhesive motifs of SCUBE1 for potential anti-thrombotic strategy.
      PubDate: Fri, 01 Mar 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz036
      Issue No: Vol. 116, No. 1 (2019)
  • Successful renal denervation decreases the platelet activation status in
           hypertensive patients
    • Authors: Zaldivia M; Hering D, Marusic P, et al.
      Pages: 202 - 210
      Abstract: AbstractAimsTo determine whether renal denervation (RDN) in hypertensive patients affects the platelet activation status.Methods and resultsWe investigated the effect of RDN on the platelet activation status in 41 hypertensive patients undergoing RDN. Ambulatory blood pressure (BP), plasma sympathetic neurotransmitter Neuropeptide Y, and platelet activation markers were measured at baseline, at 3 months, and 6 months after RDN. RDN significantly decreased BP at 3 months (150.6 ± 11.3/80.9 ± 11.4 mmHg to 144.7 ± 12.0/77.1 ± 11.1 mmHg; P < 0.01) and at 6 months (144.3 ± 13.8/78.3 ± 11.1 mmHg; P < 0.01). Plasma levels of the sympathetic neurotransmitter Neuropeptide Y, an indicator of sympathetic nerve activity, were significantly decreased at 3 months (0.29 ± 0.11 ng/mL to 0.23 ± 0.11 ng/mL; P < 0.0001) and at 6 months (0.22 ± 0.12 ng/mL; P < 0.001) after RDN. This was associated with a reduction in platelet membrane P-selectin expression (3 months, P < 0.05; 6 months, P < 0.05), soluble P-selectin (6 months, P < 0.05), circulating numbers of platelet-derived extracellular vesicles (EVs) (3 months, P < 0.001; 6 months, P < 0.01), and phosphatidylserine expressing EVs (3 months, P < 0.001; 6 months, P < 0.0001), indicative of a reduction in platelet activation status and procoagulant activity. Only patients who responded to RDN with a BP reduction showed inhibition of P-selectin expression at 3 months (P < 0.05) and 6 months (P < 0.05) as well as reduction of glycoprotein IIb/IIIa activation at 3 months (P < 0.05). Notably, 13 patients who took aspirin did not show significant reduction in platelet P-selectin expression following RDN.ConclusionOur results imply a connection between the sympathetic nervous system and the platelet activation status and provide a potential mechanistic explanation by which RDN can have favourable effects towards reducing cardiovascular complications.
      PubDate: Mon, 04 Feb 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz033
      Issue No: Vol. 116, No. 1 (2019)
  • Macrophage-derived MMP-8 determines smooth muscle cell differentiation
           from adventitia stem/progenitor cells and promotes neointima hyperplasia
    • Authors: Yang F; Chen Q, Yang M, et al.
      Pages: 211 - 225
      Abstract: AbstractAimsEmerging evidence has suggested that adventitia stem/progenitor cells (AdSPCs) migrate into the intima of arteries in response to injury, where they differentiate towards smooth muscle cells (SMCs) and participate in neointimal hyperplasia. We have previously identified matrix metalloproteinase-8 (MMP8) as a key player in atherogenesis. In this study, we aimed to investigate the functional roles of macrophage-derived MMP8 in AdSPC differentiation and injury-induced arterial remodelling.Methods and resultsWe first observed an important role for MMP8 in SMC differentiation from embryonic stem cells, but this effect was not seen in AdSPCs. Instead, through macrophages/AdSPCs co-culture and macrophage conditional culture medium studies, we have demonstrated that the MMP8 protein secreted from macrophages promotes SMC differentiation from AdSPCs. Mechanistically, we showed that macrophage-derived MMP8 promotes SMC differentiation from AdSPCs through modulating transforming growth factor-β activity and a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)/Notch1 signalling. We further demonstrated that the binding site for CBF1, Suppressor of Hairless, and Lag-1 (CSL) within SMC gene promoters is responsible for Notch1 mediated SMC differentiation. Finally, we demonstrated that macrophage-derived MMP8 increased injury-induced neointimal SMC hyperplasia by activating ADAM10/Notch1 signalling.ConclusionsWe have identified macrophage-derived MMP8 as a regulator in SMC differentiation from AdSPCs and neointimal SMC hyperplasia in response to injury. Our data provide new insights into the roles of MMP8 in AdSPC differentiation and the pathogenesis of neointima formation in the context of angiographic restenosis, and therefore may aid in the development of novel therapeutic agents for the prevention of this disease.
      PubDate: Thu, 07 Mar 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz044
      Issue No: Vol. 116, No. 1 (2019)
  • Focal TLR4 activation mediates disturbed flow-induced endothelial
    • Authors: Qu D; Wang L, Huo M, et al.
      Pages: 226 - 236
      Abstract: AbstractAimsDisturbed blood flow at arterial branches and curvatures modulates endothelial function and predisposes the region to endothelial inflammation and subsequent development of atherosclerotic lesions. Activation of the endothelial Toll-like receptors (TLRs), in particular TLR4, contributes to vascular inflammation. Therefore, we investigate whether TLR4 can sense disturbed flow (DF) to mediate the subsequent endothelial inflammation.Methods and resultsEn face staining of endothelium revealed that TLR4 expression, activation, and its downstream inflammatory markers were elevated in mouse aortic arch compared with thoracic aorta, which were absent in Tlr4mut mice. Similar results were observed in the partial carotid ligation model where TLR4 signalling was activated in response to ligation-induced flow disturbance in mouse carotid arteries, and such effect was attenuated in Tlr4mut mice. DF in vitro increased TLR4 expression and activation in human endothelial cells (ECs) and promoted monocyte-EC adhesion, which were inhibited in TLR4-knockdown ECs. Among endogenous TLR4 ligands examined as candidate mediators of DF-induced TLR4 activation, fibronectin containing the extra domain A (FN-EDA) expressed by ECs was increased by DF and was revealed to directly interact with and activate TLR4.ConclusionOur findings demonstrate the indispensable role of TLR4 in DF-induced endothelial inflammation and pinpoint FN-EDA as the endogenous TLR4 activator in this scenario. This novel mechanism of vascular inflammation under DF condition may serve as a critical initiating step in atherogenesis.
      PubDate: Wed, 20 Feb 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz046
      Issue No: Vol. 116, No. 1 (2019)
  • Adipolin/CTRP12 protects against pathological vascular remodelling through
           suppression of smooth muscle cell growth and macrophage inflammatory
    • Authors: Ogawa H; Ohashi K, Ito M, et al.
      Pages: 237 - 249
      Abstract: AbstractAimsSecreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/TNF-related protein 12, as an insulin-sensitizing adipokine. However, the role of adipolin in vascular disease remains unknown. Here, we investigated whether adipolin modulates pathological vascular remodelling.Methods and resultsAdipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery. APL-KO mice showed increased neointimal thickening after vascular injury compared with WT mice, which was accompanied by an enhanced inflammatory response and vascular cell proliferation in injured arteries. Adipolin deficiency also led to a reduction in transforming growth factor-β (TGF-β) 1 protein levels in injured arteries. Treatment of cultured macrophages with adipolin protein led to a reduction in lipopolysaccharide-stimulated expression of inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin (IL) 6, and monocyte chemotactic protein (MCP)-1. These effects were reversed by inhibition of TGF-β receptor II (TGF-βRII)/Smad2 signalling. Adipolin also reduced platelet-derived growth factor (PDGF)-BB-stimulated proliferation of vascular smooth muscle cells (VSMCs) through a TGF-βRII/Smad2-dependent pathway. Furthermore, adipolin treatment significantly increased TGF-β1 concentration in media from cultured VSMCs and macrophages.ConclusionThese data indicate that adipolin protects against the development of pathological vascular remodelling by attenuating macrophage inflammatory responses and VSMC proliferation.
      PubDate: Fri, 15 Mar 2019 00:00:00 GMT
      DOI: 10.1093/cvr/cvz074
      Issue No: Vol. 116, No. 1 (2019)
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