Natriuretic Peptides Inhibit DNA Synthesis in Cardiac Fibroblasts

Hypertension ◽  
1995 ◽  
Vol 25 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Li Cao ◽  
David G. Gardner
Keyword(s):  
Dna Synthesis ◽  
Natriuretic Peptides ◽  
Cardiac Fibroblasts

scholarly journals Paracrine effects of hypoxic fibroblast-derived factors on the MPT-ROS threshold and viability of adult rat cardiac myocytes

2008 ◽  
Vol 294 (6) ◽  
pp. H2653-H2658 ◽  
Author(s):  
K. Shivakumar ◽  
S. J. Sollott ◽  
M. Sangeetha ◽  
S. Sapna ◽  
B. Ziman ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Conditioned Medium ◽  
Cardiac Myocytes ◽  
Cytokine Production ◽  
Mitochondrial Permeability Transition ◽  
Cardiac Fibroblasts ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
Cardiac Cells ◽  
Tnf Α

Cardiac fibroblasts contribute to multiple aspects of myocardial function and pathophysiology. The pathogenetic relevance of cytokine production by these cells under hypoxia, however, remains unexplored. With the use of an in vitro cell culture model, this study evaluated cytokine production by hypoxic cardiac fibroblasts and examined two distinct effects of hypoxic fibroblast-conditioned medium (HFCM) on cardiac myocytes and fibroblasts. Hypoxia caused a marked increase in the production of tumor necrosis factor (TNF)-α by cardiac fibroblasts. HFCM significantly enhanced the susceptibility of cardiac myocytes to reactive oxygen species (ROS)-induced mitochondrial permeability transition (MPT), determined by high-precision confocal line-scan imaging following controlled, photoexcitation-induced ROS production within individual mitochondria. Furthermore, exposure of cardiac myocytes to HFCM for 5 h led to loss of viability, as evidenced by change in morphology and annexin staining. HFCM also decreased DNA synthesis in cardiac fibroblasts. Normoxic fibroblast-conditioned medium spiked with TNF-α at 200 pg/ml, a concentration comparable to that in HFCM, promoted loss of myocyte viability and decreased DNA synthesis in cardiac fibroblasts. These effects of HFCM are similar to the reported effects of hypoxia per se on these cell types, showing that hypoxic fibroblast-derived factors may amplify the distinct effects of hypoxia on cardiac cells. Importantly, because both hypoxia and oxidant stress prevail in a setting of ischemia and reperfusion, the effects of soluble factors from hypoxic fibroblasts on the MPT-ROS threshold and viability of myocytes may represent a novel paracrine mechanism that could exacerbate ischemia-reperfusion injury to cardiomyocytes.

scholarly journals Chamber-specific differences in human cardiac fibroblast proliferation and responsiveness toward simvastatin

2016 ◽  
Vol 311 (2) ◽  
pp. C330-C339 ◽  
Author(s):  
Farhan Rizvi ◽  
Alessandra DeFranco ◽  
Ramail Siddiqui ◽  
Ulugbek Negmadjanov ◽  
Larisa Emelyanova ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
Cardiac Fibrosis ◽  
Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Mrna Levels ◽  
Cycle Progression ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Fibroblasts, the most abundant cells in the heart, contribute to cardiac fibrosis, the substrate for the development of arrythmogenesis, and therefore are potential targets for preventing arrhythmic cardiac remodeling. A chamber-specific difference in the responsiveness of fibroblasts from the atria and ventricles toward cytokine and growth factors has been described in animal models, but it is unclear whether similar differences exist in human cardiac fibroblasts (HCFs) and whether drugs affect their proliferation differentially. Using cardiac fibroblasts from humans, differences between atrial and ventricular fibroblasts in serum-induced proliferation, DNA synthesis, cell cycle progression, cyclin gene expression, and their inhibition by simvastatin were determined. The serum-induced proliferation rate of human atrial fibroblasts was more than threefold greater than ventricular fibroblasts with faster DNA synthesis and higher mRNA levels of cyclin genes. Simvastatin predominantly decreased the rate of proliferation of atrial fibroblasts, with inhibition of cell cycle progression and an increase in the G0/G1 phase in atrial fibroblasts with a higher sensitivity toward inhibition compared with ventricular fibroblasts. The DNA synthesis and mRNA levels of cyclin A, D, and E were significantly reduced by simvastatin in atrial but not in ventricular fibroblasts. The inhibitory effect of simvastatin on atrial fibroblasts was abrogated by mevalonic acid (500 μM) that bypasses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition. Chamber-specific differences exist in the human heart because atrial fibroblasts have a higher proliferative capacity and are more sensitive to simvastatin-mediated inhibition through HMG-CoA reductase pathway. This mechanism may be useful in selectively preventing excessive atrial fibrosis without inhibiting adaptive ventricular remodeling during cardiac injury.

scholarly journals Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction.

1996 ◽  
Vol 98 (10) ◽  
pp. 2218-2227 ◽  
Author(s):  
N Ashizawa ◽  
K Graf ◽  
Y S Do ◽  
T Nunohiro ◽  
C M Giachelli ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Cardiac Fibroblasts ◽  
Collagen Gel ◽  
Collagen Gel Contraction

scholarly journals Stimulation of P2Y receptors activates c-fos gene expression and inhibits DNA synthesis in cultured cardiac fibroblasts

1998 ◽  
Vol 37 (3) ◽  
pp. 718-728 ◽  
Author(s):  
Jing-Sheng Zheng ◽  
Lydia O'Neill ◽  
Xilin Long ◽  
Tania E Webb ◽  
Eric A Barnard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Synthesis ◽  
Cardiac Fibroblasts ◽  
P2y Receptors ◽  
Stimulation Of
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