The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Barry H. Greenberg - One of the best experts on this subject based on the ideXlab platform.
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tumor necrosis factor α induced at1 receptor upregulation enhances angiotensin ii mediated cardiac Fibroblast responses that favor fibrosis
Circulation Research, 2002Co-Authors: Jianfeng Peng, Devorah Gurantz, Randy T Cowling, Van Tran, Barry H. GreenbergAbstract:Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase after MI and both factors affect Fibroblast functions. The type 1 (AT1) receptor that mediates most Ang II effects is upregulated after MI in cardiac Fibroblasts, and there is evidence that this is caused by TNF-α. We sought to determine if TNF-α–induced AT1 receptor upregulation alters Fibroblast responsiveness to Ang II and if this effect differs from direct TNF-α effects on Fibroblast functions. In cultured neonatal rat cardiac Fibroblasts, TNF-α reduced cellular [3H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac Fibroblasts with TNF-α–induced AT1 receptor upregulation, Ang II–stimulated [3H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated Fibroblasts. Angiotensin I...
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Tumor Necrosis Factor-α–Induced AT1 Receptor Upregulation Enhances Angiotensin II–Mediated Cardiac Fibroblast Responses That Favor Fibrosis
Circulation Research, 2002Co-Authors: Jianfeng Peng, Devorah Gurantz, Randy T Cowling, Van Tran, Barry H. GreenbergAbstract:Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase after MI and both factors affect Fibroblast functions. The type 1 (AT1) receptor that mediates most Ang II effects is upregulated after MI in cardiac Fibroblasts, and there is evidence that this is caused by TNF-α. We sought to determine if TNF-α–induced AT1 receptor upregulation alters Fibroblast responsiveness to Ang II and if this effect differs from direct TNF-α effects on Fibroblast functions. In cultured neonatal rat cardiac Fibroblasts, TNF-α reduced cellular [3H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac Fibroblasts with TNF-α–induced AT1 receptor upregulation, Ang II–stimulated [3H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated Fibroblasts. Angiotensin I...
Jianfeng Peng - One of the best experts on this subject based on the ideXlab platform.
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tumor necrosis factor α induced at1 receptor upregulation enhances angiotensin ii mediated cardiac Fibroblast responses that favor fibrosis
Circulation Research, 2002Co-Authors: Jianfeng Peng, Devorah Gurantz, Randy T Cowling, Van Tran, Barry H. GreenbergAbstract:Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase after MI and both factors affect Fibroblast functions. The type 1 (AT1) receptor that mediates most Ang II effects is upregulated after MI in cardiac Fibroblasts, and there is evidence that this is caused by TNF-α. We sought to determine if TNF-α–induced AT1 receptor upregulation alters Fibroblast responsiveness to Ang II and if this effect differs from direct TNF-α effects on Fibroblast functions. In cultured neonatal rat cardiac Fibroblasts, TNF-α reduced cellular [3H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac Fibroblasts with TNF-α–induced AT1 receptor upregulation, Ang II–stimulated [3H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated Fibroblasts. Angiotensin I...
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Tumor Necrosis Factor-α–Induced AT1 Receptor Upregulation Enhances Angiotensin II–Mediated Cardiac Fibroblast Responses That Favor Fibrosis
Circulation Research, 2002Co-Authors: Jianfeng Peng, Devorah Gurantz, Randy T Cowling, Van Tran, Barry H. GreenbergAbstract:Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase after MI and both factors affect Fibroblast functions. The type 1 (AT1) receptor that mediates most Ang II effects is upregulated after MI in cardiac Fibroblasts, and there is evidence that this is caused by TNF-α. We sought to determine if TNF-α–induced AT1 receptor upregulation alters Fibroblast responsiveness to Ang II and if this effect differs from direct TNF-α effects on Fibroblast functions. In cultured neonatal rat cardiac Fibroblasts, TNF-α reduced cellular [3H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac Fibroblasts with TNF-α–induced AT1 receptor upregulation, Ang II–stimulated [3H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated Fibroblasts. Angiotensin I...
Zhilin Qu - One of the best experts on this subject based on the ideXlab platform.
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effects of Fibroblast myocyte coupling on cardiac conduction and vulnerability to reentry a computational study
Heart Rhythm, 2009Co-Authors: Alan Garfinkel, Patrizia Camelliti, Peter Kohl, James N. Weiss, Zhilin QuAbstract:BACKGROUND: Recent experimental studies have documented that functional gap junctions form between Fibroblasts and myocytes, raising the possibility that Fibroblasts play roles in cardiac electrophysiology that extend beyond acting as passive electrical insulators. OBJECTIVE: The purpose of this study was to use computational models to investigate how Fibroblasts may affect cardiac conduction and vulnerability to reentry under different Fibroblast-myocyte coupling conditions and tissue structures. METHODS: Computational models of two-dimensional tissue with Fibroblast-myocyte coupling were developed and numerically simulated. Myocytes were modeled by the phase I of the Luo-Rudy model, and Fibroblasts were modeled by a passive model. RESULTS: Besides slowing conduction by cardiomyocyte decoupling and electrotonic loading, Fibroblast coupling to myocytes elevates myocyte resting membrane potential, causing conduction velocity to first increase and then decrease as Fibroblast content increases, until conduction failure occurs. Fibroblast-myocyte coupling can also enhance conduction by connecting uncoupled myocytes. These competing effects of Fibroblasts on conduction give rise to different conduction patterns under different Fibroblast-myocyte coupling conditions and tissue structures. Elevation of myocyte resting potential due to Fibroblast-myocyte coupling slows sodium channel recovery, which extends postrepolarization refractoriness. Owing to this prolongation of the myocyte refractory period, reentry was more readily induced by a premature stimulation in heterogeneous tissue models when Fibroblasts were electrotonically coupled to myocytes compared with uncoupled Fibroblasts acting as pure passive electrical insulators. CONCLUSIONS: Fibroblasts affect cardiac conduction by acting as obstacles or by creating electrotonic loading and elevating myocyte resting potential. Functional Fibroblast-myocyte coupling prolongs the myocyte refractory period, which may facilitate induction of reentry in cardiac tissue with fibrosis.
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Effects of Fibroblast-myocyte coupling on cardiac conduction and vulnerability to reentry: A computational study
Heart Rhythm, 2009Co-Authors: Yuanfang Xie, Patrizia Camelliti, Peter Kohl, Alan Garfinkel, James N. Weiss, Zhilin QuAbstract:Background: Recent experimental studies have documented that functional gap junctions form between Fibroblasts and myocytes, raising the possibility that Fibroblasts play roles in cardiac electrophysiology that extend beyond acting as passive electrical insulators. Objective: The purpose of this study was to use computational models to investigate how Fibroblasts may affect cardiac conduction and vulnerability to reentry under different Fibroblast-myocyte coupling conditions and tissue structures. Methods: Computational models of two-dimensional tissue with Fibroblast-myocyte coupling were developed and numerically simulated. Myocytes were modeled by the phase I of the Luo-Rudy model, and Fibroblasts were modeled by a passive model. Results: Besides slowing conduction by cardiomyocyte decoupling and electrotonic loading, Fibroblast coupling to myocytes elevates myocyte resting membrane potential, causing conduction velocity to first increase and then decrease as Fibroblast content increases, until conduction failure occurs. Fibroblast-myocyte coupling can also enhance conduction by connecting uncoupled myocytes. These competing effects of Fibroblasts on conduction give rise to different conduction patterns under different Fibroblast-myocyte coupling conditions and tissue structures. Elevation of myocyte resting potential due to Fibroblast-myocyte coupling slows sodium channel recovery, which extends postrepolarization refractoriness. Owing to this prolongation of the myocyte refractory period, reentry was more readily induced by a premature stimulation in heterogeneous tissue models when Fibroblasts were electrotonically coupled to myocytes compared with uncoupled Fibroblasts acting as pure passive electrical insulators. Conclusions: Fibroblasts affect cardiac conduction by acting as obstacles or by creating electrotonic loading and elevating myocyte resting potential. Functional Fibroblast-myocyte coupling prolongs the myocyte refractory period, which may facilitate induction of reentry in cardiac tissue with fibrosis. © 2009 Heart Rhythm Society.
Stanley Nattel - One of the best experts on this subject based on the ideXlab platform.
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congestive heart failure effects on atrial Fibroblast phenotype differences between freshly isolated and cultured cells
PLOS ONE, 2012Co-Authors: Kristin Dawson, Chiatung Wu, Xiao Yan Qi, Stanley NattelAbstract:INTRODUCTION: Fibroblasts are important in the atrial fibrillation (AF) substrate resulting from congestive heart failure (CHF). We previously noted changes in in vivo indices of Fibroblast function in a CHF dog model, but could not detect changes in isolated cells. This study assessed CHF-induced changes in the phenotype of Fibroblasts freshly isolated from control versus CHF dogs, and examined effects of cell culture on these differences. METHODS/RESULTS: Left-atrial Fibroblasts were isolated from control and CHF dogs (ventricular tachypacing 240 bpm × 2 weeks). Freshly-isolated Fibroblasts were compared to Fibroblasts in primary culture. Extracellular-matrix (ECM) gene-expression was assessed by qPCR, protein by Western blot, Fibroblast morphology with immunocytochemistry, and K(+)-current with patch-clamp. Freshly-isolated CHF Fibroblasts had increased expression-levels of collagen-1 (10-fold), collagen-3 (5-fold), and fibronectin-1 (3-fold) vs. control, along with increased cell diameter (13.4 ± 0.4 µm vs control 8.4 ± 0.3 µm) and cell spreading (shape factor 0.81 ± 0.02 vs. control 0.87 ± 0.02), consistent with an activated phenotype. Freshly-isolated control Fibroblasts displayed robust tetraethylammonium (TEA)-sensitive K(+)-currents that were strongly downregulated in CHF. The TEA-sensitive K(+)-current differences between control and CHF Fibroblasts were attenuated after 2-day culture and eliminated after 7 days. Similarly, cell-culture eliminated the ECM protein-expression and shape differences between control and CHF Fibroblasts. CONCLUSIONS: Freshly-isolated CHF and control atrial Fibroblasts display distinct ECM-gene and morphological differences consistent with in vivo pathology. Culture for as little as 48 hours activates Fibroblasts and obscures the effects of CHF. These results demonstrate potentially-important atrial-Fibroblast phenotype changes in CHF and emphasize the need for caution in relating properties of cultured Fibroblasts to in vivo systems.
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molecular determinants of cardiac Fibroblast electrical function and therapeutic implications for atrial fibrillation
Cardiovascular Research, 2011Co-Authors: Stanley NattelAbstract:Cardiac Fibroblasts account for about 75% of all cardiac cells, but because of their small size contribute only ∼10–15% of total cardiac cell volume. They play a crucial role in cardiac pathophysiology. For a long time, it has been recognized that Fibroblasts and related cell types are the principal sources of extracellular matrix (ECM) proteins, which organize cardiac cellular architecture. In disease states, Fibroblast production of increased quantities of ECM proteins leads to tissue fibrosis, which can impair both mechanical and electrical function of the heart, contributing to heart failure and arrhythmogenesis. Atrial fibrosis is known to play a particularly important role in atrial fibrillation (AF). This review article focuses on recent advances in understanding the molecular electrophysiology of cardiac Fibroblasts. Cardiac Fibroblasts express a variety of ion channels, in particular voltage-gated K+ channels and non-selective cation channels of the transient receptor potential (TRP) family. Both K+ and TRP channels are important determinants of Fibroblast function, with TRP channels acting as Ca2+-entry pathways that stimulate Fibroblast differentiation into secretory myoFibroblast phenotypes producing ECM proteins. Fibroblasts can couple to cardiomyocytes and substantially affect their cellular electrical properties, including conduction, resting potential, repolarization, and excitability. Co-cultured preparations of cardiomyocytes and Fibroblasts generate arrhythmias by a variety of mechanisms, including spontaneous impulse formation and rotor-driven reentry. In addition, the excess ECM proteins produced by Fibroblasts can interrupt cardiomyocyte-bundle continuity, leading to local conduction disturbances and reentrant arrhythmias. A better understanding of the electrical properties of Fibroblasts should lead to an improved comprehension of AF pathophysiology and a variety of novel targets for antiarrhythmic intervention.
Devorah Gurantz - One of the best experts on this subject based on the ideXlab platform.
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tumor necrosis factor α induced at1 receptor upregulation enhances angiotensin ii mediated cardiac Fibroblast responses that favor fibrosis
Circulation Research, 2002Co-Authors: Jianfeng Peng, Devorah Gurantz, Randy T Cowling, Van Tran, Barry H. GreenbergAbstract:Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase after MI and both factors affect Fibroblast functions. The type 1 (AT1) receptor that mediates most Ang II effects is upregulated after MI in cardiac Fibroblasts, and there is evidence that this is caused by TNF-α. We sought to determine if TNF-α–induced AT1 receptor upregulation alters Fibroblast responsiveness to Ang II and if this effect differs from direct TNF-α effects on Fibroblast functions. In cultured neonatal rat cardiac Fibroblasts, TNF-α reduced cellular [3H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac Fibroblasts with TNF-α–induced AT1 receptor upregulation, Ang II–stimulated [3H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated Fibroblasts. Angiotensin I...
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Tumor Necrosis Factor-α–Induced AT1 Receptor Upregulation Enhances Angiotensin II–Mediated Cardiac Fibroblast Responses That Favor Fibrosis
Circulation Research, 2002Co-Authors: Jianfeng Peng, Devorah Gurantz, Randy T Cowling, Van Tran, Barry H. GreenbergAbstract:Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase after MI and both factors affect Fibroblast functions. The type 1 (AT1) receptor that mediates most Ang II effects is upregulated after MI in cardiac Fibroblasts, and there is evidence that this is caused by TNF-α. We sought to determine if TNF-α–induced AT1 receptor upregulation alters Fibroblast responsiveness to Ang II and if this effect differs from direct TNF-α effects on Fibroblast functions. In cultured neonatal rat cardiac Fibroblasts, TNF-α reduced cellular [3H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac Fibroblasts with TNF-α–induced AT1 receptor upregulation, Ang II–stimulated [3H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated Fibroblasts. Angiotensin I...
