心力衰竭(HF)的特征在于进行性纤维化。成纤维细胞和间充质干细胞(MSC)都可以分化成促纤维化肌成纤维细胞。MSCs分泌和表达血小板源性生长因子(PDGF)及其受体。我们假设心脏MSCs(cMSCs)中的PDGF信号促进其肌成纤维细胞分化,并加重心肌梗死后左心室重构和纤维化。我们表明,心肌梗死后心脏衰竭的cMSC表现出改变的表型。抑制PDGF信号在体外抑制cMSC-肌成纤维细胞分化,而在建立的缺血性HF期间的体内抑制减轻了左心室重构和功能,减少心肌纤维化,肥大,和炎症。因此,调节cMSCPDGF受体表达可能代表了一种限制HF病理性心脏纤维化的新方法。
Heart failure (HF) is characterized by progressive fibrosis. Both fibroblasts and mesenchymal stem cells (MSCs) can differentiate into pro-fibrotic myofibroblasts. MSCs secrete and express platelet-derived growth factor (PDGF) and its receptors. We hypothesized that PDGF signaling in cardiac MSCs (cMSCs) promotes their myofibroblast differentiation and aggravates post-myocardial infarction left ventricular remodeling and fibrosis. We show that cMSCs from failing hearts post-myocardial infarction exhibit an altered phenotype. Inhibition of PDGF signaling in vitro inhibited cMSC-myofibroblast differentiation, whereas in vivo inhibition during established ischemic HF alleviated left ventricular remodeling and function, and decreased myocardial fibrosis, hypertrophy, and inflammation. Modulating cMSC PDGF receptor expression may thus represent a novel approach to limit pathologic cardiac fibrosis in HF.