经皮冠状动脉介入（PCI）术后管腔再狭窄发生率高。血管内膜增生是其重要的病理基础。血管平滑肌细胞（VSMCs）增殖迁移可引起内膜增生。骨成型蛋白4（BMP-4）参与调控血管功能。前期研究表明大鼠颈动脉损伤后出现内膜增生，成熟型和非成熟型BMP-4表达增高，血浆BMP-4活性升高，拮抗BMP-4活性抑制血管损伤后内膜增生；BMP-4促进VSMCs增殖迁移，BMP-4抑制剂拮抗由BMP-4表达升高引起的VSMCs增殖迁移。因此我们提出研究课题：研究BMP-4通过调控VSMCs增殖迁移促进血管损伤后内膜增生的机制。本课题将应用电生理学和分子生物学等手段阐明①BMP-4表达变化在血管损伤后内膜增生中的生物学意义；②BMP-4促进VSMCs增殖迁移的分子机制（BMP-4-Kv1.5-CaMKⅡδ）；③拮抗BMP-4对损伤后血管内膜增生的防治作用。本课题为PCI术后再狭窄的防治提供新靶点和理论依据。

Neointimal hyperplasia is the major cause of restenosis after percutaneous coronary intervention, which is associated with the proliferation and migration of vascular smooth muscle cells (VSMCs). It is reported that bone morphogenetic protein-4 (BMP-4) influencen blood vessel behavior. Our previous study showed balloon injury significantly stimulated arterial neointimal formation in SD rat, compared with sham carotids, BMP-4 expression and serum activity were markedly upregulated, BMP-4 inhibitor prevented neointimal formation; BMP-4 promoted proliferation and migration of VSMCs, BMP-4 inhibitor Noggin inhibited VSMCs proliferation and migration which induced by BMP-4. Therefore, We put forward the hypothethsis : BMP-4 promoted neointimal hyperplasia through increasing proliferation and migration of VSMCs. we will use a series of molecularbiological and electrophysiological techniques to carry out the following research: ①The effect of BMP-4 on neointimal hyperplasia after balloon injury; ②The role of BMP-4 which have been shown to regulate cell cycle and MMPs expression, in proliferation and migration of VSMCs; ③ The role of inhibition of BMP-4 protein expression in neointimal hyperplasia after injury. This project will provided the new drug target and theoretical basis for prevention and treatment restenosis after percutaneous coronary intervention.