Cardiovascular Research (CARDIOVASC RES )

Publisher: British Medical Association; British Cardiac Society; European Society of Cardiology, Elsevier

Description

Cardiovascular Research is the International Basic Science Journal of the European Society of Cardiology. The Journal is concerned with both basic and clinical research in the field of cardiovascular physiology and pathophysiology. The Journal welcomes submission of papers both at the molecular, subcellular, cellular, organ and organism level, and of clinically oriented papers offering insight into (patho)physiological mechanisms.

  • Impact factor
    5.81
    Show impact factor history
     
    Impact factor
  • 5-year impact
    6.11
  • Cited half-life
    7.00
  • Immediacy index
    1.69
  • Eigenfactor
    0.05
  • Article influence
    1.93
  • Website
    Cardiovascular Research website
  • Other titles
    Cardiovascular research, CVR
  • ISSN
    0008-6363
  • OCLC
    1553351
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

Elsevier

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers
    • Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository
    • Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists
    • Set statement to accompany deposit
    • Published source must be acknowledged
    • Must link to journal home page or articles' DOI
    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • NIH Authors articles will be submitted to PMC after 12 months
    • Authors who are required to deposit in subject repositories may also use Sponsorship Option
    • Pre-print can not be deposited for The Lancet
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: AIMS: Mutations in KCNQ1, encoding for Kv7.1, the α-subunit of the IKs channel, cause long-QT syndrome type 1 (LQTS1), potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular during elevated sympathetic tone. Here we aim at characterizing the p.Lys557Glu (K557E) Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked) increased adrenergic tone. METHODS AND RESULTS: K557E carriers had moderate QTc prolongation that augmented significantly during exercise. IKs characteristics were determined after co-expressing Kv7.1-wildtype (WT) and/or K557E with minK and Yotiao in Chinese hamster ovary (CHO) cells. K557E caused IKs loss-of-function with slowing of the activation kinetics, acceleration of deactivation kinetics, and a rightward shift of voltage-dependent activation. Combined, these contributed to a dominant-negative reduction in IKs density. Confocal microscopy and Western blot indicated that trafficking of K557E channels was not impaired. Stimulation of WT IKs by cAMP generated strong current upregulation that was preserved for K557E in both hetero- and homozygosis. Accumulation of IKs at fast rates occurred both in WT and K557E, but was blunted in the latter. In a computational model, K557E showed a loss of action-potential shortening during β-adrenergic stimulation, in accordance with the lack of QT shortening during exercise in patients. CONCLUSIONS: K557E causes IKs loss-of-function with reduced fast-rate-dependent current accumulation. cAMP-dependent stimulation of mutant IKs is preserved, but incapable of fully compensating for the baseline current reduction, explaining the long QT intervals at baseline and the abnormal QT accommodation during exercise in affected patients.
    Cardiovascular Research 08/2014;
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    ABSTRACT: Aims Pulmonary arterial hypertension (PAH) reflects abnormal pulmonary vascular resistance and causes right ventricular (RV) hypertrophy. Enhancement of the late sodium current (INaL), may result from hypertrophic remodeling. The study tests whether: 1) constitutive INaL enhancement may occur as part of PAH-induced myocardial remodelling; 2) ranolazine (RAN), a clinically available INaL blocker, may prevent constitutive INaL enhancement and PAH-induced myocardial remodelling. Methods and Results PAH was induced in rats by a single monocrotaline injection (MCT, 60 mg/Kg i.p.); studies were performed 3 weeks later. RAN (30 mg/Kg bid i.p.) was administered 48 hrs after MCT and washed-out 15 hrs before studies. MCT increased RV systolic pressure, caused RV hypertrophy and loss of LV mass. In the RV, collagen was increased, myocytes were enlarged with T-tubules disarray, displayed myosin heavy chain isoform switch. INaL was markedly enhanced; diastolic Ca2+ was increased and Ca2+ release was facilitated. K+ currents were downregulated and APD was prolonged. In the LV, INaL was enhanced to a lesser extent and cell Ca2+ content was strongly depressed. Electrical remodelling was less prominent than in the RV. RAN completely prevented INaL enhancement and limited most aspects of PAH-induced remodeling, but failed to affect in-vivo contractile performance. RAN blunted the MCT-induced increase in RV pressure and medial thickening in pulmonary arterioles. Conclusions PAH induced remodeling with chamber-specific aspects. RAN prevented constitutive INaL enhancement and blunted myocardial remodeling. Partial mechanical unloading, resulting from an unexpected effect of RAN on pulmonary vasculature, might contribute to this effect.
    Cardiovascular Research 08/2014;
  • Cardiovascular Research 07/2014; 103(1).
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Currently, progenitor cells and tissue engineering are being proposed as an addition to conventional therapies of myocardial infarction. Engineered tissue grafts and myocardial bioprostheses aim to improve cellular engraftment and viability, combining cellular components with supporting materials. Here, we proposed a new bioprosthesis composed by human pericardial-derived scaffold and adipose tissue progenitor cells (ATPCs) for human cardiac repair. METHODS: Surgical samples of human pericardium were obtained from 39 patients (27 males, 12 females; mean age 68±11 years; range 50 to 84 years) undergoing cardiothoracic surgery, with apparently healthy pericardia. For decellularization, a protocol combining detergents, enzymatic digestion and agitation was used and remaining DNA was quantified by spectrophotometry. Decellularized pericardia were lyophilized by drying under vacuum, sterilized by gamma irradiation and analyzed by scanning electron microscopy. To assess in vitro degradation, lyophilized scaffolds were incubated with 0.1% collagenase I. Recellularization was carried out by mixing equal volume of cell suspension (GFP+-ATPCs in 10% sucrose) with hydrogel (RAD16-I 0.3% in 10% sucrose). In vitro biocompatibility was tested by loading hydrogel (with or without GFP+-ATPCs) in the pericardial scaffolds and then cultured 1 week under standard conditions. Masson's trichrome staining was performed to verify recellularization and cell viability was analyzed with a commercial kit. RESULTS: After decellularization, human pericardia were pale collagen scaffolds free of cellular debris and rich in filaments. Total DNA content within the acellular scaffold was significantly lower (P=0.012) than that obtained for native pericardium (66±24 ng DNA/mg scaffold vs. 214±79 ng DNA/mg pericardium, respectively). Nuclei staining with Hoechst 33342 confirmed no residual nucleic acids in decellularized pericardium. Furthermore, biodegradability experiments showed that scaffolds lost ~70% of their original weight after collagenase I treatment (P<0.001). After 1 week of recellularization, the majority of GFP+-ATPCs remained viable inside the bioprosthesis. CONCLUSIONS: Decellularization protocol efficiently removed all cellular and nuclear material of human pericardial tissue. In addition, evidences of biocompatibility and biodegradation of the resulting bioprosthesis were further provided in vitro. This pericardial-based bioprosthesis could be deliverable via currently used, minimally invasive methods, to promote cell homing into damaged myocardium.
    Cardiovascular Research 07/2014; 103(Suppl 1):143.
  • Cardiovascular Research 07/2014; 103(Supplement 1):P324.
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Cardiac tissue engineering emerges as a promising alternative to current therapies addressed to myocardial infarction. In this context, we aimed to obtain and characterize myocardial bioprosthesis based on a decellularized matrix capable of being engrafted in damaged myocardium. METHODS: Myocardial blocks (3x3 cm), differentiating epicardial, mesocardial and endocardial regions, were obtained from cadaveric porcine hearts (n=5) and decellularized using two different protocols: Protocol 1 (P1) combines chemical (ionic and non-ionic detergents), enzymatic (DNase) and physical (agitation) treatments, and Protocol 2 (P2) is based on a combination of chemical (non-ionic detergent, acid, hypotonic and hypertonic solutions), enzymatic (trypsin) and physical (agitation) procedures. Decellularization level was assessed histologically (Masson's Trichrome stain and immunohistochemistry) and molecularly (DNA quantification). The resulting acellular structure was examined by scanning electron microscopy. Extracellular matrix components were analyzed by immunohistochemistry and local matrix stiffness was determined by measuring the Young's modulus with atomic force microscopy. Biodegradability of decellularized matrices was evaluated in vitro with collagenase treatment. RESULTS: Total absence of cells after decellularization was confirmed by Trichrome staining and immunohistochemistry. DNA content was significantly reduced in both protocols (P1: 86.0±1.7%, P2: 96.3±1.1%, compared to native tissue; p<0.001), with significant differences between them (p<0.001). Remarkably, integrity of matrix filaments was preserved due the presence of type-I collagen and elastin. Mechanical testing revealed no significant changes in stiffness of decellularized matrices when compared to native tissue (Native: 27.5±4.9, P1: 33.0±10.7, P2: 40.0±7.1 kPa; p=0.55). The biodegradability assay also confirmed complete degradation of matrices without differences among protocols (Weight loss: P1: 90.1±5.4%, P2: 93.8±5.1%; p=0.19). Finally, non-significant differences were found in epicardial, mesocardial and endocardial decellularized blocks in terms of cells removal, structural, proteical or mechanical characterization. CONCLUSIONS: Acellular myocardial matrices were successfully obtained by both decellularization protocols, preserving major structural components so as mechanical and biodegradability properties.Furthermore, trypsin-based protocol (P2) yielded less DNA residues which could contribute to prevent rejection.
    Cardiovascular Research 07/2014; 103(Suppl 1):93.
  • Cardiovascular Research 07/2014; 103(1).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Recent evidence suggests cardiac progenitor cells (CPC) may improve cardiac function after injury. The underlying mechanisms are indirect, but their mediators remain unidentified. Exosomes and other secreted membrane vesicles, hereafter collectively referred to as extracellular vesicles (EVs), act as paracrine signalling mediators. Here we report that EVs secreted by human CPCs are crucial cardioprotective agents. Methods and Results CPCs were derived from atrial appendage explants from patients who underwent heart valve surgery. CPC conditioned medium inhibited apoptosis in mouse HL-1 cardiomyocytic cells, while enhancing tube formation in human umbilical vein endothelial cells. These effects were abrogated by depleting conditioned medium of EVs. They were reproduced by EVs secreted by CPCs, but not by those secreted by human dermal fibroblasts. Transmission electron microscopy and nanoparticle tracking analysis showed most EVs to be 30-90 nm in diameter, the size of exosomes, although smaller and larger vesicles were also present. microRNAs most highly enriched in EVs secreted by CPCs compared to fibroblasts included miR-210, miR-132, and miR-146a-3p. miR-210 downregulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. miR-132 downregulated its target, RasGAP-p120, enhancing tube formation in endothelial cells. Infarcted hearts injected with EVs from CPCs, but not from fibroblasts, exhibited less cardiomyocyte apoptosis, enhanced angiogenesis, and improved LV ejection fraction (0.8±6.8% vs. –21.3±4.5%; p<0.05) compared to those injected with control medium. Conclusion EVs is the active component of the paracrine secretion by human CPCs. As a cell-free approach, EVs could circumvent many of the limitations of cell transplantation.
    Cardiovascular Research 07/2014; 10.1093/cvr/cvu167.
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    ABSTRACT: INTRODUCTION: Chronic angiotensin converting enzyme inhibitor (ACEIs) treatment can suppress arrhythmogenesis. To examine whether the effect is more immediate and independent of suppression of pathological remodelling, we tested the antiarrhythmic effect of short-term ACE inhibition in healthy normotensive rats. METHODS AND RESULTS: Wistar rats were administered with enalaprilat (ENA, i.p., 5 mg/kg every 12 h) or vehicle (CON) for two weeks. Cellular shortening was measured in isolated, electrically paced cardiomyocytes. Standard 12-lead electrocardiography was performed and, hearts of anesthetized open-chest rats were subjected to 6-min ischemia followed by 10-minute reperfusion to examine susceptibility to ventricular arrhythmias. Expressions of calcium regulating proteins (SERCA2a, cardiac sarco/endoplasmic reticulum Ca2+-ATPase; CSQ, calsequestrin; TRD, triadin; PLB, phospholamban; FKBP12.6, FK506-binding protein) were measured by Western blot and mRNA levels of L-type calcium channel (Cacna1c), ryanodine receptor (Ryr2) and potassium channels Kcnh2 and Kcnq1 were measured by qRT-PCR. ENA decreased systolic as well as diastolic blood pressure (by 20%, and by 31%, respectively, for both P<0.05) but enhanced shortening of cardiomyocytes at basal conditions (by 34%, P<0.05) and under beta-adrenergic stimulation (by 73%, P<0.05). Enalaprilat shortened QTc interval duration (CON: 78±1 ms vs. ENA: 72±2 ms; P<0.05) and significantly decreased the total duration of ventricular fibrillations (VF) and the number of VF episodes (P<0.05). Reduction in arrhythmogenesis was associated with a pronounced upregulation of SERCA2a and increased Cacna1c mRNA levels. CONCLUSION: Short-term ACEI treatment can provide protection against I/R injury-induced ventricular arrhythmias in healthy myocardium and this effect is associated with increased SERCA2a expression. cardiovascres;103/suppl_1/S78/CHAPTERSUB75653TB1T1CHAPTERsub-75653TB1 CON ENA Calcium regulating proteins SERCA2a 100±20 304±13* CSQ 100±6 105±7 TRD 100±16 117±10 PLB 100±9 109±16 FKBP12 100±12 93±7.
    Cardiovascular Research 06/2014;
  • Cardiovascular Research 06/2014;
  • Cardiovascular Research 05/2014;
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    ABSTRACT: Aim. Nitric oxide (NO) plays a key role in vascular homeostasis and is produced by endothelial NO synthase (eNOS), encoded by NOS3 gene. We previously reported the genetic association between NOS3 rs753482-A>C polymorphism on intron 19 and coronary artery disease (CAD). In the attempt of conferring functional implication to the rs753482-A>C polymorphism, we investigated its influence on transcript maturation. Methods and Results. A transcript variant skipping exons 20-21 is prevalent in carriers of the rs753482-C allele and is translated in a novel truncated form of eNOS. The truncated eNOS displays increased basal NO production, is insensitive to calcium stimulation, and, upon heterodimerization with the full-length eNOS protein, exerts a dominant-negative effect on NO production. CAD patients and healthy subjects carriers of the rs753482-C genotype are characterized by increased NO basal levels in peripheral blood and platelets, and negatively respond to oral glucose load by failing to increase NO synthesis following insulin wave. Furthermore, forearm vasodilation after reactive hyperemia is dramatically impaired in rs753482-C carriers. Conclusions. We demonstrated that subjects carrying the rs753482-C genotype express a novel stable truncated form of eNOS with altered enzymatic activity that influences NO production and endothelial function. These findings open to new intriguing perspectives to several diseases involving vascular response to NO.
    Cardiovascular Research 12/2013; 100(3).
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    ABSTRACT: AIMS: Urotensin-II (UII) is a vasoactive peptide that promotes vascular smooth muscle cells (VSMCs) proliferation and is involved in the pathogenesis of atherosclerosis, restenosis and vascular remodeling. This study aimed to determine the role of calcium (Ca2+)-dependent signaling and alternative signaling pathways in UII-evoked VSMCs proliferation focussing on store-operated Ca2+ entry (SOCE) and epithelium growth factor receptor (EGFR) transactivation. METHODS AND RESULTS: We used primary cultures of VSMCs isolated from wistar rat aorta to investigate the effects of UII on intracellular Ca2+ mobilization, and proliferation determined by 5-bromo-2-deoxyuridine (BrdU) assay. We found that UII enhanced intracellular Ca2+ concentration ([Ca2+]i) which was significantly reduced by classical SOCE inhibitors and by knockdown of essential components of the SOCE such as STIM1, Orai1, or TRPC1. Moreover, UII activated a Gd3+-sensitive current with similar features of the Ca2+ release-activated Ca2+ current (ICRAC). Additionally, UII stimulated VSMCs proliferation and Ca2+/cAMP response element-binding protein (CREB) activation through SOCE pathway that involved STIM1, Orai1, and TRPC1. Co-immunoprecipitation experiments showed that UII promoted the association between Orai1 and STIM1, and between Orai1 and TRPC1. Moreover, we determined that epithelium growth factor receptor (EGFR) transactivation, extracellular signal-regulated kinase (ERK) and Ca2+/calmodulin-dependent kinase (CaMK) signaling pathways were involved in both UII-mediated Ca2+ influx, CREB activation and VSMCs proliferation. CONCLUSION: Our data show for the first time that UII-induced VSMCs proliferation and CREB activation requires a complex signaling pathway that involves on the one hand SOCE mediated by STIM1, Orai1 and TRPC1, and on the other hand EGFR, ERK, and CaMK activation.
    Cardiovascular Research 08/2013;
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    ABSTRACT: Connexins form a family of transmembrane proteins that consists of 20 members in humans and 21 members in mice. Six connexins assemble into a connexon that can function as a hemichannel or connexon that can dock to a connexon expressed by a neighboring cell, thereby forming a gap junction channel. Such intercellular channels synchronize responses in multicellular organisms through direct exchange of ions, small metabolites and other second messenger molecules between the cytoplasms of adjacent cells. Multiple connexins are expressed in the cardiovascular system. These connexins not only experience the different biomechanical forces within this system but may also act as effector proteins in coordinating responses within groups of cells towards these forces. This review discusses recent insights regarding regulation of cardiovascular connexins by mechanical forces and junctions. It specifically addresses effects of i) shear stress on endothelial connexins, ii) hypertension on vascular connexins and iii) changes in afterload and the composition of myocardial mechanical junctions on cardiac connexins.
    Cardiovascular Research 04/2013;

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