PPARβ/δ activation inhibits angiotensin II-induced collagen type I expression in rat cardiac fibroblasts

Peroxisome proliferator-activated receptors (PPARα, β/δ and γ) are nuclear receptors and PPARγ activation was previously reported to inhibit collagen expression in the heart, but whether PPARβ/δ also regulates collagen expression in the heart remains unclear. In this study, we investigated the effect of PPARβ/δ activation on angiotensin II (Ang II)-induced collagen type I expression in adult rat cardiac fibroblasts. The results showed that PPARβ/δ was expressed at the moderate level in cardiac fibroblasts. GW501516, a selective PPARβ/δ 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 PPARβ/δ via RNA interference. In summary, we find that PPARβ/δ is present in cardiac fibroblasts and PPARβ/δ activation inhibits Ang II-induced collagen type I expression at least in part via decreasing collagen synthesis. PPARβ/δ may be a promising therapeutic target for myocardial fibrosis.