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).
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    ABSTRACT: Several cardiomyopathies, including myocardial ischemia, have been associated with an impairment of gap junction intercellular communication (GJIC) between cardiomyocytes, due to an increased internalization and/or degradation of Connexin43 (Cx43). Recent data of our group, demonstrates that ischemia-induced activation of autophagy results in degradation of Cx43 in HL-1 cells. However, the molecular mechanisms underlying Cx43 degradation and the involvement of autophagy machinery remain unknown. It is broadly accepted that autophagy have a dichotomous role likely depending on the nature, extent and severity of the stimuli, as well as on the autophagy players involved. The emerging theory stands for a cardioprotective role of ischemia-induced autophagy via AMPK, being up-regulation of Beclin1 associated with exacerbated autophagy and cell death. Hence, it is conceivable to suggest that according to the stimuli (ischemia vs ischemia/reperfusion (I/R)), the triggering signals and mechanisms whereby autophagy is activated may differ and, consequently, determine the degradation levels of Cx43. To test this hypothesis, we used HL-1 cardiomyocytes subjected to different periods of ischemia and I/R, after which the levels and subcelullar distribution of Cx43 were determined by WB and confocal microscopy, respectively. Data show that Cx43 is degraded gradually during ischemia, and that reperfusion further increases its degradation. Furthermore, using chemical and genetic approaches to manipulate AMPK and Beclin-1 pathways, we showed that activation of AMPK occurs in the initial periods of ischemia, when an inhibition of AMPK protects Cx43 from degradation. On the other hand, for long periods of ischemia and during reperfusion, the protective effect regarding Cx43 degradation is mainly conferred by knockdown of Beclin 1. Concerning autophagy activation, we show that conversion of LC3-I in LC3-II occurs mainly during I/R, which is consistent with the increased degradation of Cx43 under these conditions. Interaction of Cx43 with autophagy adaptors during ischemia and I/R was also evaluated by immunoprecipitation assays and confocal microscopy. Increased interaction with autophagy players p62 and LC3 is mainly detected upon ischemia, which is likely required for the subsequent robust degradation of Cx43 observed during reperfusion. Altogether, our data led us to suggest a model in which differential activation of autophagy in ischemia and I/R, involving either AMPK or Beclin1, respectively, determines the final fate of Cx43.
    Cardiovascular Research 07/2014; 103(suppl 1):S25.
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    ABSTRACT: Hypertension and/or aging impose stress on the heart with consecutive cardiac hypertrophy, inflammation and fibrosis, processes that lead to heart failure. Our group has previously shown that non-structural matrix proteins such as TSP-2 and SPARC are critical during hypertension, fibrosis, and age-related cardiac dysfunction. Osteoglycin (OGN) is a class III member of the small leucine rich proteoglycans, and was recently identified as a marker of increased left ventricular mass in a study using genomics in recombinant inbred hypertensive rat strains. Its precise biological role in cardiac remodeling, however, remains unclear. We hypothesize that OGN will influence cardiac hypertrophy and fibrosis and hence is critical in the cardiac response during hypertension and aging. We show in young adult mice (3 months old) that hypertension-induced pressure overload of the heart causes two phases of cardiac fibrosis, following 28 days of angiotensin-II (AngII) infusion. The first phase develops between days 3 to 7 after the AngII-treatment and consists of diffuse interstitially deposited loose fibers. During the second wave of fibrosis, which starts at 14 days, these loose fibers transition into more localized scars of denser collagens. Interestingly, the expression of OGN mRNA also shows a biphasic response, significantly decreasing prior to each phase of fibrosis, at day 1 (96% decrease, p=0.002) and day 14 (84% decrease, p=0.004) respectively. Moreover, hypertension causes exaggerated cardiac fibrosis (7.54±1.58 vs. 3.65±0.62 %, p=0.04) and increased heart weight to body weight ratios (6.39±0.31 vs. 5.42±0.17 mg/g, p=0.01) in young adult OGN null mice when compared to WT littermates, but no differences in the amount of infiltrating leukocytes (31.48±9.82 vs. 36.32±18.75 cells/mm(2)), after 28 days of AngII infusion. In addition, aging results in decreased cardiac function, as measured by ejection fraction, in 18 months versus 3 months old OGN null mice (42.65±2.74 vs. 58.05±1.37 %, p=0.0001), which is absent in WT mice (51.01±3.11 vs. 53.01±1.67 %, p=0.62). Furthermore, a follow-up study in WT and OGN null mice showed a decrease in stroke volume over time in the OGN null mice (39.30±2.90 μl at 6 months, 35.54±1.95 μl at 12 months and 31.13±1.29 μl at 18 months, p=0.04 between 6 and 18 months) but not in the WT mice (41.61±2.02 μl at 6 months, 39.04±1.95 μl at 12 months and 41.04±3.05 μl at 18 months). Collectively, these data suggest that OGN regulates cardiac fibrosis during pressure overload and is therefore important in the remodeling response to hypertension and aging.
    Cardiovascular Research 07/2014; 103(suppl 1):S54.
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    ABSTRACT: Oxidative stress plays a key role in cardiac diseases, although the sources of reactive oxygen species (ROS) have not been defined conclusively. Recent studies demonstrated that the mitochondrial enzymes monoamine oxidases (MAO) are a major source of ROS in reperfusion injury and decompensated hypertrophy. The present study characterized the molecular mechanisms responsible for the increased activity of MAO. Based upon available information, the activity of these enzymes depends mostly on substrate availability. Therefore, we aimed at identifying the major substrates of MAO in hearts undergoing oxidative stress. Mass spectrometry was used to identify and quantitate potential substrates by comparing their contents in the absence and the presence of MAO inhibition.
    Cardiovascular Research 07/2014; 103(suppl 1):S4.
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    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.
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    ABSTRACT: Mechanisms underlying atrial fibrillation (AF) the most common cardiac arrhythmia in aged population are not fully elucidated. We have previously shown that unlike to young the aged guinea pig heart is much prone to develop AF upon repetitive burst stimulation. We hypothesize that in addition to atrial structural remodeling the alterations in cardiac cell-to-cell coupling due to the ageing may facilitate induction and persistence of AF.
    Cardiovascular Research 07/2014; 103(suppl 1):S6.
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    ABSTRACT: Accumulation of DNA damage due to impaired base excision repair (BER) may play a role in the pathogenesis of myocardial failure. The DNA glycosylase Neil3 is known to carry out BER during oxidative stress induced DNA damage, but is also thought to have a role in stem cell biology. Based on this, we hypothesized that Neil3 plays a role in myocardial remodeling during heart failure (HF). qPCR showed an increased expression of Neil3 in myocardial biopsies from patients with severe HF, and that the Neil3 expression significantly decreased following improvement of myocardial function following treatment with left ventricular assist device. In a murine model of myocardial infarction (MI) we found a strong upregulation of Neil3 on day 3, 7 and 21 after MI. At day 7, myocardial cell isolation revealed a low Neil3 expression in cardiomyocytes, while a 2.5- and a 4.5-fold increased expression was found in endothelial cells and fibroblasts, respectively, following MI compared to sham. In leukocytes an equally high expression of Neil3 was observed in both sham and MI. Using Neil3 knock-out (KO) mice we found a significantly higher mortality in KO compared to wild type (WT) mice after MI ( 73% vs. 40%), despite smaller infarct sizes in the Neil3 KO, as determined by MRI. The first week post MI, all animals died from cardiac rupture. Zymography on protein extracts from the infarcted tissue revealed significantly increased levels of MMP2 in the Neil3 KO, 3 days after MI. Immunohistochemistry (IHC), at the same time point, showed similar numbers of inflammatory cells measured by the presence of Ly6G+ neutrophils, Mac2+ monocytes/macrophages and CD45+ leukocytes. At day 6 a significantly higher number of Ki67+ proliferating cells were observed in the Neil3 KO infarcted areas. In accordance with this, primary cardiac fibroblasts lacking Neil3 showed a higher proliferation rate, measured both by BrdU and scrape wound assay. Furthermore, we found a significantly higher mRNA expression of both the myofibroblast marker α-SMA, and collagen type III in cardiac fibroblasts isolated from Neil3 KO mice 7 days post MI, indicating increased levels of activated fibroblasts and altered fibroblast function. IHC 6 days post MI showed the same tendency towards more α-SMA-positive fibroblasts and more collagen by Sirius red in the Neil3 KO infarcts, however these differences were not statistically significant. In conclusion, our data suggest that after MI, Neil3 plays a role in regulating fibroblast proliferation and function, affecting wound healing and extracellular matrix composition and quality, altogether reducing mortality.
    Cardiovascular Research 07/2014; 103(suppl 1):S88.
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    ABSTRACT: Recent evidences have shown that phenolic structures can exert many biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. In this study we aimed to investigate the effect of EA on cardiac Ca2+ currents and contractility in rat ventricular myocytes and to elucidate the underlying mechanisms of these changes. All records measured from the freshly isolated ventricular myocytes of rat heart at 36±1 °C by using whole-cell configuration of voltage clamp. Cell shortening was measured by detecting the length of edges with video-based system at 1 Hz frequency of field stimulation. We found that EA dose dependently reduced Ca2+ currents with EC50= 23 nM. EA decreased voltage dependent L-type Ca2+ current density (ICaL) but it didn't affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase (AC) with SQ-22536 (10 μM) and using probucol (antioxidant, 5 μM) had no effect on EA modulation of ICaL. Interestingly, blockage of nitric oxide synthase (NOS) with L-NAME (500 μM) and guanylate cyclase (GC) with ODQ (1 μM) abolished inhibitory effect of EA on ICaL. Moreover, EA dose dependently blunted fractional shorthening of ventricular myocytes. In conclusion, EA affects ionic and mechanical properties of ventricular myocytes starting at nanomolar concentrations. Our findings indicated that EA suppresses ICaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathway. Accordingly, EA may be useful in pathophysiological conditions whereby these effects might be favorable such as hypertension and ischemic heart diseases.
    Cardiovascular Research 07/2014; 103(suppl 1):S22.
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    ABSTRACT: Microtubules are highly dynamic polymers present in eukaryote cells that are essential components of cell cytoskeleton. They play an important role in intracellular transport, in maintaining organelle organization and function, and in transmitting mechanical forces within the myocardium. However, this intracellular network becomes disrupted during myocardial ischemia/reperfusion, and it has been proposed that microtubule disruption is an early sign of irreversible ischemic injury, and that prevention of microtubule disruption during ischemia-reperfusion could be beneficial. In this study we aimed to assess the effects of prevention of microtubule disruption with paclitaxel on ischemia/reperfusion injury in both isolated rat cardiomyocytes and isolated, Langendorff-perfused, rat hearts.
    Cardiovascular research; 07/2014
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    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).
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    ABSTRACT: In ventricular myocytes of rodents, ryanodine receptors (RyRs) are typically organized at Z-lines where the sarcoplasmic reticulum forms dyads with T-tubules (TTs). In large mammals, TT density is lower and not all RyRs are coupled to the TTs. Recently, we have shown that non-coupled RyRs lack a CaMKII and ROS-dependent microdomain modulation during rate adaptation. Here we examine how this microdomain modulation may be altered in ischemic cardiomyopathy where the fraction of non-coupled RyRs is increased.
    Cardiovascular Research 07/2014; 103(suppl 1):S8.