Abstract:
AIMS:We investigated the molecular mechanism of rapid-depolarization-induced atrial fibrosis. METHODS AND RESULTS:We used a direct atrial myocyte-fibroblast contact co-culture and a fibroblast-specific transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF) and procollagen type I α-1 (COL1A1) luciferase reporter system to investigate the possible molecular mechanism of rapid-depolarization-induced atrial fibrosis. Mouse atrial fibroblasts were first transfected with promoter-luciferase reporters, and then co-cultured with HL-1 atrial myocytes. Rapid depolarization of atrial myocytes by rapid electrical field stimulation induced increased TGF-β1, CTGF and COL1A1 promoter activities in the co-cultured atrial fibroblasts (2.4 ± 0.3-fold increase, P= 0.008 for TGF-β1; 2.9 ± 0.4-fold increase, P< 0.001 for CTGF; and 2.1 ± 0.2-fold increase, P= 0.008 for COL1A1). Rapid depolarization of atrial myocytes increased paracrine secretion of angiotensin II (Ang II) and reactive oxygen species in the co-culture medium. Rapid electrical field stimulation-induced ROS generation in atrial myocytes was attenuated by the membrane NADPH oxidase inhibitor, apocynin. Atrial myocyte-induced expression of TGF-β1, CTGF and COL1A1 in atrial fibroblasts was attenuated by co-treatment with the Ang II receptor blocker, losartan, and apocynin. Atrial myocyte-induced COL1A1 expression in atrial fibroblasts was attenuated by anti-TGF-β1 antibody and RNA interference knockdown of the TGF-β1 receptor. CONCLUSION:We first demonstrated that tachycardia of atrial myocytes induced paracrine secretion of Ang II and reactive oxygen species, which in turn induced expression of CTGF and procollagen in co-cultured atrial fibroblasts through increasing TGF-β1 expression. The results may imply that use of an Ang II receptor blocker, in combination with an anti-oxidant, blocks rapid-depolarization-induced atrial fibrosis.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Tsai CT,Tseng CD,Hwang JJ,Wu CK,Yu CC,Wang YC,Chen WP,Lai LP,Chiang FT,Lin JLdoi
10.1093/cvr/cvq322subject
Has Abstractpub_date
2011-03-01 00:00:00pages
805-15issue
4eissn
0008-6363issn
1755-3245pii
cvq322journal_volume
89pub_type
杂志文章abstract:OBJECTIVES:To determine whether the cytokine cardiotrophin-1 (CT-1) can protect the adult heart against ischaemia/reperfusion when added either prior to ischaemia or at reperfusion. BACKGROUND:CT-1 has previously been shown to protect cultured embryonic or neonatal cardiocytes from cell death. To assess the therapeuti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00531-4
更新日期:2002-03-01 00:00:00
abstract:STUDY OBJECTIVE:The aim of the study was to determine whether the deleterious effects of anaesthesia on cardiac muscle function were due to disturbance of protein synthesis. Comparative investigations were made on anaerobic and aerobic skeletal muscles, and plasma insulin and growth hormone levels were also measured to...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.4.314
更新日期:1991-04-01 00:00:00
abstract:OBJECTIVE:Angiotensin II (ANG II) has recently been reported to increase inotropy in adult rabbit myocytes by a mechanism of alkalinization and consequent increased myofilament sensitivity to calcium. Accordingly, we tested the hypothesis that ANG II would have a greater inotropic effect during ischemic conditions than...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00185-x
更新日期:1997-01-01 00:00:00
abstract::To evaluate the effect of beta blockade on energy metabolism in ischaemic myocardium metoprolol tartrate in doses of 0.2 or 0.5 mg.kg-1 or saline was injected into 24 anaesthetised dogs 20 min after coronary ligation. Regional myocardial blood flow was measured by the hydrogen gas clearance method, and the heart rate ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.9.660
更新日期:1987-09-01 00:00:00
abstract:OBJECTIVE:To characterise the effect of coronary intra-arterial thrombosis upon the downstream vascular bed. BACKGROUND:The vascular response downstream from a coronary intra-arterial thrombus has not previously been characterised. We postulated that downstream vasoconstriction might result from the presence of endoth...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract:AIMS:Cardiac hypertrophy is a risk factor independent of blood pressure; however, the mechanisms that distinguish pathological remodelling due to local cues from pressure overload are unresolved. This study was aimed at discovering a novel gene expression mechanism in heart failure. METHODS AND RESULTS:In angiotensin ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp285
更新日期:2010-01-01 00:00:00
abstract:AIMS:Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key compone...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt265
更新日期:2014-03-01 00:00:00
abstract::The effects of L-propionylcarnitine on the recovery of cardiac contractile performance after global ischaemia and reperfusion were studied in isolated perfused rat hearts. The addition of either 5.5 or 11 mmol X litre-1 L-propionylcarnitine significantly improved the recovery of cardiac output, left ventricular pressu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.7.536
更新日期:1986-07-01 00:00:00
abstract::Physical training has been advocated to minimize the problems associated with coronary heart disease; however, the responsible mechanisms are obscure. Rats trained to run on a treadmill were subjected to acute conditions of hypoxia and myocardial ischaemia. Trained rats were better able to maintain a higher level of c...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.3.359
更新日期:1976-05-01 00:00:00
abstract::Ischemic preconditioning is a well-established phenomenon first described in experimental preparations in which brief episodes of ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce myocardial infarct size. There are ample correlates of ischemic preconditioning in the clinical realm. Precon...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.01.012
更新日期:2006-05-01 00:00:00
abstract:OBJECTIVE:This study investigated whether endothelial dysfunction occurs in mesenteric arteries of apoE-deficient mice and determined the role of endothelin (ET)-1, which is increased in human atherosclerosis, using an orally active endothelin ET(A) receptor antagonist. METHODS:ApoE-deficient and C57BL/6J control mice...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00469-2
更新日期:2002-02-01 00:00:00
abstract::To examine how end systole differs from end ejection and also whether the slope of the end systolic pressure-volume relation can be approximated to that of the end ejection pressure-volume relation, nine isolated, perfused, paced canine hearts ejecting into a hydraulic loading system that simulated the aortic input im...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.2.107
更新日期:1987-02-01 00:00:00
abstract::An analytical formulation has been developed which allows the computation of mitral valve area (A) from the potentially noninvasive paramaeters of hear rate (R), cardiac output (CO) and diastolic filling period (DFP) by the equation A = 21 CO/R x DFP2. The computed areas correlate with autopsy and open heart measureme...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.4.223
更新日期:1980-04-01 00:00:00
abstract:AIMS:Despite their ability to cause septic shock and myocardial dysfunction, components of Gram-negative bacterial cell walls, like lipopolysaccharide, have been shown in numerous studies to induce myocardial protection during ischaemia-reperfusion injury. Muramyl dipeptide (MDP) is another such component recognized by...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp055
更新日期:2009-07-15 00:00:00
abstract:AIMS:It is well established that leukotrienes (LTs), products of the 5-lipoxygenase (5-LO) pathway, participate in inflammatory tissue reactions and immune responses. In the present study, the impact of the 5-LO pathway on vasculogenesis of mouse embryonic stem (ES) cells was investigated. METHODS AND RESULTS:Immunohi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp385
更新日期:2010-04-01 00:00:00
abstract::The genetic basis of cardiac electrical phenotypes has in the last 25 years been the subject of intense investigation. While in the first years, such efforts were dominated by the study of familial arrhythmia syndromes, in recent years, large consortia of investigators have successfully pursued genome-wide association...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa144
更新日期:2020-07-15 00:00:00
abstract::The mechanical, haemodynamic, and energetic functions of isolated perfused working hearts from chronic alcoholic and control rats were studied. Male Long-Evans rats were fed a nutritionally-complete liquid diet containing 38% of daily calories as ethanol (isocaloric replacement with dextrin-maltose for controls) for 3...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.3.136
更新日期:1979-03-01 00:00:00
abstract:AIMS:Adverse cardiovascular events in humans occur with a day/night pattern, presumably related to a daily pattern of behaviours or endogenous circadian rhythms in cardiovascular variables. Healthy humans possess a scale-invariant/fractal structure in heartbeat fluctuations that exhibits an endogenous circadian rhythm ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn150
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:To study the effect of cardiac contraction on left coronary artery pressure-flow relations at different vascular volumes and to compare these relations in the beating heart with those in the heart arrested in systole and diastole. METHODS:Maximally vasodilated, Tyrode perfused, rabbit hearts (n = 6) with an ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00119-9
更新日期:1998-10-01 00:00:00
abstract::CaMKII is a serine-threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflamm...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw002
更新日期:2016-04-01 00:00:00
abstract:AIMS:Recent immunohistochemical studies observed the loss of plakoglobin (PG) from the intercalated disc (ID) as a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), suggesting a final common pathway for this disease. However, the underlying molecular processes are poorly understood. METHODS AND RESUL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq353
更新日期:2011-04-01 00:00:00
abstract::Hydrogen sulfide (H2S), as a gaseous signalling molecule, has been found to play important roles in postconditioning (PostC)-induced cardioprotection. Similar to nitric oxide (NO)-mediated protein S-nitrosylation (SNO), recent studies suggest that H2S could regulate protein function through another redox-based post-tr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw037
更新日期:2016-05-01 00:00:00
abstract:Aims:Endothelial hyperpermeability exacerbates multiple organ damage during inflammation or infection. The endothelial glycocalyx, a protective matrix covering the luminal surface of endothelial cells (ECs), undergoes enzymatic shedding during inflammation, contributing to barrier hyperpermeability. A disintegrin and m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy167
更新日期:2018-11-01 00:00:00
abstract:OBJECTIVES:Angiotensin converting enzyme (ACE) activity in the plasma does not change significantly with hypertension in two-kidney, one-clip hypertensive (2K-1C) rats. However, heart ACE activity and mRNA increase with hypertension. We measured the ACE activity and mRNA in hypertrophied hearts at different times after...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract:AIMS:Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms. METHODS AND RESULT...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy257
更新日期:2019-03-15 00:00:00
abstract:OBJECTIVE:Inhibitors of poly (ADP-ribose) synthetase (PARS) activity reduce the infarct size caused by regional myocardial ischaemia and reperfusion in the rabbit and rat in vivo. The mechanism of action of these inhibitors is unclear. Here we investigate the effects of the PARS inhibitor 3-aminobenzamide (3-AB) on inf...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00221-1
更新日期:1999-01-01 00:00:00
abstract:OBJECTIVES:I(Ks), the slow component of the delayed rectifier potassium current, underlies a strong beta-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in I(Ks). Recent work has pointed to an opposing biological effect of beta(1)- and beta(3)-adrenoceptors in the heart....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00601-6
更新日期:2002-12-01 00:00:00
abstract:OBJECTIVE:We have previously demonstrated that nuclear factor kappa B (NFkappaB) activation is needed for the development of cardiac hypertrophy in vivo. NFkappaB is a downstream transcription factor in the Toll-like receptor (TLR)-mediated signaling pathway; therefore, we investigated a role of TLR4 in cardiac hypertr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.025
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVE:Activin-like kinase receptor 1 (ALK1) is a transforming growth factor (TGF)-beta type I receptor expressed in vascular mesenchyme, yet its function in vascular mesenchymal cells (VMC) is unclear. We examined ALK1 expression in human coronary atherosclerotic lesions and bovine and human VMC undergoing cellular...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.09.014
更新日期:2007-05-01 00:00:00
abstract:AIMS:Exercise capacity is reduced in heart failure (HF) patients, due mostly to skeletal muscle abnormalities including impaired energy metabolism, mitochondrial dysfunction, fibre type transition, and atrophy. Glucagon-like peptide-1 (GLP-1) has been shown to improve exercise capacity in HF patients. We investigated t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw182
更新日期:2016-09-01 00:00:00