[5-19]Dedifferentiated Smooth Muscle Cells Promote Atherosclerosis: Role of STAT1-mediated Vascular Inflammation

报告题目：Dedifferentiated Smooth Muscle Cells Promote Atherosclerosis: Role of STAT1-mediated Vascular Inflammation
报 告 人：何朝勇 博士（美国俄克拉荷马医学研究所）
报告时间：2015年5月19日（星期二）上午9:00
报告地点：独墅湖校区二期云轩楼2301室

报告人简介：
何朝勇博士于2005年12月获中国协和医科大学博士学位，2005年至2008年在北京大学基础医学院药理学系任讲师，2008-2011在美国俄克拉荷马大学医学中心医学系进行博士后研究，2011起在美国俄克拉荷马医学研究所任研究科学家和高级研究科学家。何朝勇博士现为美国科学促进会、美国实验病理学会等学会会员。何朝勇博士同时担任欧洲药理学报（European Journal of Pharmacology）、糖尿病&代谢（Diabetes & Metabolism）、临床和实验药理学和生理学（Clinical and Experimental Pharmacology and Physiology）糖尿病&肥胖和代谢（Diabetes, Obesity and Metabolism）等多个SCI 收录杂志特约审稿人。何朝勇博士的研究兴趣集中于心血管和内分泌疾病，如动脉粥样硬化、糖尿病、肥胖的分子机制以及药物治疗靶点的研究。何朝勇博士在国际权威期刊如 Nature Communications, Diabetes, Circulation Research, Autophagy，American journal of Pathology  等一流杂志发表论文数篇。
报告摘要：
Atherosclerosis remains the leading cause of death in developed countries. Understanding the molecular mechanisms that lead to the development of atherosclerosis will enable us to explore new therapeutic interventions to protect against atherosclerosis. Studies have revealed that many different cell types including endothelial cells, immune cells and vascular smooth muscle cells (SMCs) are involved in atherosclerotic lesion formation. Platelet derived growth factor (PDGF) has been known to be a potent chemoattractant and mitogen for SMCs and it is thought to contribute to atherogenesis because expression of PDGF and its receptors is increased in lesions of atherosclerosis. Recent evidence suggests there are additional functions for the PDGF signaling pathway in atherosclerosis. We have used a mouse genetics approach to address this question. In our newly developed knockin mouse model (SM-PDGFRbD849V), PDGF receptor β (PDGFRβ) signaling is increased specially in developing vascular SMCs. After crossing into ApoE-/- background, these mice developed accelerated aortic lesion and coronary atherosclerosis that resemble advanced human atherosclerosis. Mechanistically, we discovered that signal transducer and activator of transcription 1 (STAT1) is constitutively activated in SMCs from SM-PDGFRbD849V mice. Intriguely, activation of STAT1 in SMCs was found to be associated with downregulation of SMC differentiation markers, enhanced gene expression of chemokines and extracellular matrix, and increased lymphocyte recruitment into aortic wall. Moreover, inhibition of PDGF signaling attenuated STAT1 activation in SMCs.  Knockout of STAT1 abolished PDGF signaling induced chemokine and matrix gene upregualtion. Our observations demonstrate PDGF signaling promotes initiation and progression of atherosclerosis and STAT1 could be a new therapeutic target for atherosclerosis.