Elevated expression of connective tissue growth factor in human atrial fibrillation and angiotensin II-treated cardiomyocytes
Journal
Circulation Journal
Journal Volume
75
Journal Issue
7
Pages
1592-1600
Date Issued
2011
Author(s)
Abstract
Background: Atrial fibrosis is a feature of structural remodeling in atrial fibrillation (AF). Connective tissue growth factor (CTGF) is a potent profibrotic factor, but its role of CTGF in AF is not yet fully understood. Methods and Results: Right atrial appendages were obtained from 20 patients who underwent cardiac surgery (10 with sinus rhythm, 10 with AF). The mRNA level, protein level and immunohistochemical staining of CTGF were significantly increased in AF patients. In a porcine AF model, tissue angiotensin II (Ang II) and CTGF levels were significantly upregulated in both atria. In perfused rat hearts, Ang II stimulation increased CTGF expression, which could be inhibited by Ang II type I receptor antagonist. In a cell culture system, both atrial fibroblasts and myocytes were responsible for the increased CTGF expression under Ang II treatment. Ang II type I receptor antagonist could inhibit the Ang II-induced CTGF expression. Treating with recombinant CTGF, atrial fibroblasts expressed an increased level of collagen I. Furthermore, the CTGF level was highly correlated with tissue Ang II content in AF pigs. Conclusions: AF patients and animals exhibited a significantly increased expression of CTGF. Ang II stimulation upregulated CTGF expression in both atrial fibroblasts and myocytes. Ang II-induced CTGF expression might be involved in atrial substrate remodeling.
SDGs
Other Subjects
1 (4 dimethylamino 3 methylbenzyl) 5 diphenylacetyl 4,5,6,7 tetrahydro 1h imidazo[4,5 c]pyridine 6 carboxylic acid; angiotensin II; collagen type 1; connective tissue growth factor; losartan; messenger RNA; recombinant connective tissue growth factor; recombinant growth factor; telmisartan; unclassified drug; adult; aged; animal cell; animal experiment; animal model; animal tissue; article; cell stimulation; clinical article; controlled study; gene expression; heart atrium appendage; heart atrium fibrillation; heart muscle cell; heart muscle fibrosis; heart perfusion; heart surgery; human; human tissue; immunohistochemistry; myofibroblast; newborn; nonhuman; pathophysiology; protein analysis; protein expression; protein induction; rat; sinus rhythm; swine; tissue level; Aged; Aged, 80 and over; Angiotensin II; Animals; Atrial Fibrillation; Cells, Cultured; Collagen; Connective Tissue Growth Factor; Disease Models, Animal; Extracellular Matrix; Female; Fibroblasts; Heart Atria; Humans; Male; Middle Aged; Myocytes, Cardiac; Rats; Rats, Wistar; RNA, Messenger; Swine
Type
journal article