Elevated expression of connective tissue growth factor in human atrial fibrillation and angiotensin II-treated cardiomyocytes

Wen Chin Ko, Chuang Ye Hong, Shaw Min Hou, Chien-Huang Lin, Eng Thiam Ong, Chwen Fang Lee, Chia Ti Tsai, Ling Ping Lai

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40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1592-1600
Number of pages9
JournalCirculation Journal
Volume75
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Keywords

  • Angiotensin ii
  • Atrial fibrillation
  • Connective tissue growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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