Abstract：
:Cardiac fibrosis is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure and cardiac arrhythmias. However the specific cells and signaling pathways mediating this process are poorly understood. Lysine acetylation of nucleosomal histone tails is an important mechanism for the regulation of gene expression. Additionally, proteomic studies have revealed that thousands of proteins in all cellular compartments are subject to reversible lysine acetylation, and thus it is becoming clear that this post-translational modification will rival phosphorylation in terms of biological import. Acetyl groups are conjugated to lysine by histone acetyltransferases (HATs) and removed from lysine by histone deacetylases (HDACs). Recent studies have shown that pharmacologic agents that alter lysine acetylation by targeting HDACs have the remarkable ability to block pathological fibrosis. Here, we review the current understanding of cardiac fibroblasts and the fibrogenic process with respect to the roles of lysine acetylation in the control of disease-related cardiac fibrosis. Potential for small molecule HDAC inhibitors as anti-fibrotic therapeutics that target cardiac fibroblasts is highlighted. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium."
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Schuetze KB,McKinsey TA,Long CSdoi
10.1016/j.yjmcc.2014.02.015subject
Has Abstractpub_date
2014-05-01 00:00:00pages
100-7eissn
0022-2828issn
1095-8584pii
S0022-2828(14)00074-1journal_volume
70pub_type
杂志文章,评审abstract：:The protection of ischemic preconditioning (PC) appears to be triggered by activation of receptors which couple to protein kinase C (PKC) during the brief ischemia. Previous experiments, however, suggest that phosphorylation of PKC's substrates is not required for the myocytes to enter the preconditioned state. Becaus...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0344
更新日期：1997-03-01 00:00:00
abstract：AIMS:Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activi...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2017.07.001
更新日期：2017-08-01 00:00:00
abstract：:To determine the regulatory role of prolyl hydroxylation in intracellular cardiac procollagen turnover, we examined the effects of prolyl 4-hydroxylase inhibitors (alpha, alpha-dipyridil, 3,4-dihydroxybenzoic acid ethyl ester, pyridine 2,4-dicarboxylic acid ethyl ester) and ascorbic acid on procollagen metabolism by c...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(95)90095-0
更新日期：1995-08-01 00:00:00
abstract：:Fluorescein isothiocyanate-conjugated lectins (FTC-lectins) have been used to study the occurrence and the distribution of their receptors in the coating of mouse myocardial cells throughout their differentiation (from 10 days post-coitum to the adult stage). FTC-Con A, -WGA and -PNA specifically inhibited by alpha-ma...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(83)90285-7
更新日期：1983-02-01 00:00:00
abstract：:The cardiac voltage-gated Na(+) channel, Na(V)1.5, is responsible for the upstroke of the action potential in cardiomyocytes and for efficient propagation of the electrical impulse in the myocardium. Even subtle alterations of Na(V)1.5 function, as caused by mutations in its gene SCN5A, may lead to many different arrh...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2015.02.013
更新日期：2015-05-01 00:00:00
abstract：:Structural and morphological changes of the cardiovascular systems (cardiovascular remodeling) are a major clinical outcome of cardiovascular diseases. Many lines of evidences have implied that transfiguration of reduction/oxidation (redox) homeostasis due to excess production of reactive oxygen species (ROS) and/or R...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2014.02.003
更新日期：2014-08-01 00:00:00
abstract：:The importance of the Na+/K+/Cl- co-transport system of the rat myocardial sarcolemma was studied under hypothermic ischemia by investigating the effect of the co-transport blockers furosemide and bumetanide on the sodium influx into the myocardium. The intracellular Na+ accumulation during hypothermic ischemia was fo...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1993.1157
更新日期：1993-12-01 00:00:00
abstract：:We have identified in soluble extracts of rat heart, a 500 000 dalton sulfhydryl-dependent protease which degrades globin and casein to acid-soluble peptides at an alkaline pH optimum. This enzyme was purified more than 1700-fold with respect to the postmicrosomal supernatant. On the basis of various catalytic and bio...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(83)90304-8
更新日期：1983-01-01 00:00:00
abstract：:Adult rat heart was dissociated into a single-cell suspension by a retrograde perfusion technique with collagenase and hyaluronidase in Krebs-Ringer phosphate buffer. Long-term culture of these isolated single cardiac muscle cells was established for up to 45 days. Transmission electron microscopy and immunofluorescen...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(83)91342-1
更新日期：1983-05-01 00:00:00
abstract：:Neural structures have been shown to be present in valve cusp tissue. We aimed to characterise the influence of neuronal stimulation on the component structures of the aortic root and cusps. Specimens of sinus, sinotubular junction (STJ), annulus and cusp tissue were dissected from porcine aortic roots and either stim...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2008.03.014
更新日期：2008-06-01 00:00:00
abstract：:Diabetes mellitus is associated with an increased incidence and greater severity of primary atherosclerosis as well as restenosis after angioplasty for reasons not yet clear. We have shown previously that insulin and proinsulin-typically elevated in blood in patients with type II diabetes-increase plasma activity of p...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0719
更新日期：1998-08-01 00:00:00
abstract：:We studied the presence of collagen degrading enzymes (matrix metalloproteinases, MMPs) in porcine myocardium following ischemia and late reperfusion. In nine pigs, left anterior descending coronary artery was occluded for 6 h followed by reperfusion for 3 h. Six pigs without coronary occlusion served as controls. Aft...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0711
更新日期：1998-07-01 00:00:00
abstract：:The volume of blood in the left ventricular wall increases as coronary perfusion pressure or coronary blood flow increase, but it is unclear whether such an increase in volume can acutely alter the diastolic pressure-dimension relationship of the intact, working left ventricle. In 19 dogs, we measured left ventricular...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(86)80966-x
更新日期：1986-06-01 00:00:00
abstract：:Heart and skeletal muscle cells rapidly lose potassium ions after withdrawal of oxygen. In myocardial ischemia, cellular release of potassium and interruption of extracellular washout produce a rapid and marked increase of extracellular K+ concentration. Harris et al. were the first to observe the coincidence of the K...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(87)80608-9
更新日期：1987-10-01 00:00:00
abstract：:Although the myocardium is capable of utilizing both glucose and fatty acid substrates, glucose metabolism is inhibited in the presence of fatty acid during normal perfusion conditions. Fatty acid regulation of glucose utilization in intact beating rat hearts was studied with 13C-enriched substrates and 13C and 31P NM...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(89)90787-6
更新日期：1989-05-01 00:00:00
abstract：:We examined changes in expression and function of the cardiac Na+, K(+)-pump in a post-infarction rat model of hypertrophy and congestive heart failure (CHF). Myocardial infarction was induced by ligation of the left coronary artery in Wistar rats and hearts were obtained from animals with CHF and from sham operated r...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0696
更新日期：1998-07-01 00:00:00
abstract：:The existing literature indicates a crucial role of p38 MAP (mitogen-activated protein) kinase (p38MAPK) and its downstream target MAPKAP kinase 2 (MK2) in ischemic preconditioning (IPC). Accordingly, deletion of MK2 gene should abolish the cardioprotective ability of IPC. Interestingly, we were able to partially prec...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,收录出版
doi：10.1016/j.yjmcc.2007.02.010
更新日期：2007-05-01 00:00:00
abstract：:There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive. In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxyge...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0850
更新日期：1999-01-01 00:00:00
abstract：:Lysophosphatidylcholine (LPC) accumulation in intracellular and/or interstitial space in cardiomyocytes may underlie as a mechanism for tachycardia and various arrhythmias during cardiac ischemia, which is usually accompanied by elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)). The present study was there...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2009.08.032
更新日期：2010-01-01 00:00:00
abstract：:Congenital heart block (CHB) affects offspring of mothers with autoantibodies (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is associated with high morbidity and mortality. Here, we show that maternal anti-Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcolemma, recognize huma...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2001.1379
更新日期：2001-06-01 00:00:00
abstract：:Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that extracellular signal-regulated kinase (ERK) 1/2 ac...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2014.06.018
更新日期：2014-10-01 00:00:00
abstract：:The mechanisms responsible for myocardial dysfunction in the setting of sepsis remain undefined. Fas ligation with its cognate ligand (FasL) induces apoptosis and activates cellular inflammatory responses associated with tissue injury. We determined whether interruption of Fas/FasL interaction by cardiac-specific expr...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2007.09.016
更新日期：2008-01-01 00:00:00
abstract：:The effects of cytochalasin D, a specific F-actin depolymerizing agent, on Ca2+ transients in rat ventricular cardiomyocytes were investigated. Cytochalasin D (20 microM) significantly slowed decay of Ca2+ transients (tau decay control cells=28.1+/-1.3, n=28tau decay=47.3+/-2.8 ms, n=20, P<0.001). The rising phase of ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0715
更新日期：1998-08-01 00:00:00
abstract：:Human hearts with idiopathic dilated cardiomyopathy have diminished adenylate cyclase activity and increased amounts of the alpha-subunit of the inhibitory guanine nucleotide-binding regulatory protein (alpha Gi) as measured by pertussis toxin catalyzed ADP-ribosylation. We utilized specific antisera against synthetic...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(91)90168-l
更新日期：1991-04-01 00:00:00
abstract：OBJECTIVE:The function of the C-terminus region of the human ether-a-go-go related gene (HERG) has not been well characterized except for its involvement in trafficking. To understand further the role of C-terminus region, we performed a functional analysis of a novel frameshift mutation (1122fs/147) identified in a Ja...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2004.09.010
更新日期：2004-12-01 00:00:00
abstract：:The opening of mitochondrial permeability transition pore (PTP) during reperfusion injury of heart has been well demonstrated and thus controlling PTP would attenuate the myocardial damage and cell death. Ursodeoxycholic acid (UDCA) is a hydrophilic bile salt and has been shown to prevent apoptosis in hepatocytes by i...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.07.014
更新日期：2005-11-01 00:00:00
abstract：:Growing evidence suggests that the beta1-adrenoceptor-directed autoimmune mechanism may play an important role in the pathogenesis of idiopathic dilated cardiomyopathy. The aim of this study is to further study the effect of specific immunoabsorption of anti-beta1-adrenoceptor autoantibodies on cardiac structure and f...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2006.04.016
更新日期：2006-07-01 00:00:00
abstract：:Cardiac tyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied left ventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibition prevents both hypertrophy and fibrosis. In a normal heart, the TRH increase induces fibrosis and hypertrophy opening the question of whether TRH could be a c...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.09.009
更新日期：2018-11-01 00:00:00
abstract：:Aspirin and clopidogrel are used therapeutically for their anti-platelet effects. We examined the effects of aspirin and clopidogrel on basal and beta-adrenoceptor (beta-AR)-mediated platelet nitric oxide (NO) synthesis in healthy subjects and patients with coronary heart disease (CHD). Healthy subjects (n=19) were ra...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.yjmcc.2008.05.015
更新日期：2008-08-01 00:00:00
abstract：:Endothelial cells responses to a variety of agonists include release of endothelium dependent vasodilators, such as endothelium dependent relaxing factor (EDRF) and prostacyclin (PGI2). These substances act on vascular smooth muscle to cause relaxation and also have potent anti-aggregatory effects on platelets. A stud...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(89)90841-9
更新日期：1989-02-01 00:00:00
