Blockade of platelet‐derived growth factor on cardiac fibrogenic response (1152.10)

Abstract

Interstitial fibrosis appears in the viable myocardium of the infarcted heart (MI) and contributes to ventricular dysfunction. Platelet‐derived growth factor (PDGF) is a family of growth factors that stimulates cell growth, differentiation and migration. Our previous study has shown that PDGF‐D and PDGF receptors (PDGFR) were increased in the viable myocardium of the infarcted heart and cells expressing PDGF/PDGFR were predominantly fibroblasts. Herein, we sought to determine whether PDGF is involved in the development of interstitial fibrosis in the infarcted heart. MI was induced by the left coronary artery ligation in rats with or without receiving PDGF receptor antagonist (imatinib, 40mg/kg/d). Sham‐operated rats served as controls. We detected the effect of PDGF blockade on cardiac collagen synthesis and degradation at one week postMI. We found that compared to controls, TGF‐β1, type I collagen, TIMP‐1, TIMP‐2, MMP‐2 and MMP‐9 expressions were significantly increased in the viable myocardium of the left ventricle. PDGFR blockade significantly attenuated TGF‐β1, type I collagen, TIMP‐1/‐2 and MMP‐2 expressions compared to MI rats. These observations indicate that PDGF plays a role in the development of interstitial fibrosis in the viable myocardium of the infarcted heart. Our findings suggest the potential therapeutic effect of PDGFR blockade on interstitial fibrosis in the infarcted heart.Grant Funding Source: NIH