PPARbeta/delta activation inhibits angiotensin II-induced collagen type I expression in rat cardiac fibroblasts

• Published in: Archives of biochemistry and biophysics 2007-04, Vol.460 (1), p.25-32
• Main Authors: Zhang, Huijie, Pi, Rongbiao, Li, Ruifang, Wang, Ping, Tang, Futian, Zhou, Sigui, Gao, Jie, Jiang, Jianmin, Chen, Shaorui, Liu, Peiqing
• Format: Article
• Language: English
• Subjects: Angiotensin II - antagonists & inhibitors; Angiotensin II - pharmacology; Animals; Collagen Type I - metabolism; Dose-Response Relationship, Drug; Fibroblasts - drug effects; Fibroblasts - metabolism; Male; Myocardium - cytology; PPAR delta - agonists; PPAR delta - metabolism; PPAR-beta - agonists; PPAR-beta - metabolism; Rats; Rats, Sprague-Dawley; RNA Interference; Thiazoles - pharmacology
• ISSN: 0003-9861

Peroxisome proliferator-activated receptors (PPARalpha, beta/delta and gamma) are nuclear receptors and PPARgamma activation was previously reported to inhibit collagen expression in the heart, but whether PPARbeta/delta also regulates collagen expression in the heart remains unclear. In this study, we investigated the effect of PPARbeta/delta activation on angiotensin II (Ang II)-induced collagen type I expression in adult rat cardiac fibroblasts. The results showed that PPARbeta/delta was expressed at the moderate level in cardiac fibroblasts. GW501516, a selective PPARbeta/delta agonist, depressed Ang II-stimulated collagen type I expression and collagen synthesis in cardiac fibroblasts in a concentration-dependent manner. Furthermore, these inhibitory effects of GW501516 were completely reversed by the knockdown of PPARbeta/delta via RNA interference. In summary, we find that PPARbeta/delta is present in cardiac fibroblasts and PPARbeta/delta activation inhibits Ang II-induced collagen type I expression at least in part via decreasing collagen synthesis. PPARbeta/delta may be a promising therapeutic target for myocardial fibrosis.