MVP调控血管损伤后内皮细胞线粒体自噬的作用及机制研究

PCI术后血管再狭窄严重影响患者临床治疗效果和术后生活治量。血管内皮细胞损伤是术后血管内膜新生引起再狭窄的始动环节，增强内皮细胞抵抗损伤的能力可减缓PCI术后血管内膜新生，拮抗血管再狭窄，但目前对于血管内膜新生中内皮细胞的抗损伤机制尚不完全清楚。我们初步预实验研究发现，穹窿主体蛋白MVP可通过结合线粒体自噬通路关键蛋白Parkin，促进线粒体自噬发生和保护线粒体功能，从而保护血管内皮细胞，减轻有害因素引起的内皮细胞损伤。本项目拟在此基础上，进一步构建内皮细胞MVP特异性敲除小鼠，建立颈动脉结扎模型，结合分子生物学实验及临床人群样本研究，深入探讨MVP调控线粒体自噬拮抗内皮细胞损伤的机制，拟发现防治PCI引起血管再狭窄新的分子干预靶点。

Restenosis after PCI is the most prominent pathological issue limiting the prognoses and postoperative life management of patients. Vascular endothelial cells injury is the initial of the arterial neointima formation, the hallmark of restenosis. Enhancing the ability of endothelial cells to resist injury may be a useful strategy for slowing down neointima formation and antagonizing restenosis after PCI. However, the precise anti-injury mechanisms of vascular endothelial cells in neointima formation are not fully understood. Our preliminary experimental data found that MVP could bind with Parkin, a key protein in the mitophagy pathway, to promote mitophagy and mitochondrial function, so as to protect vascular endothelial cells and reduce the damage of endothelial cells caused by harmful factors. This project was further planned to explore the regulatory roles of MVP in anti-injury mechanisms of endothelial cells via the models of endothelial cell MVP specific knockout mice with carotid artery ligation model, combining cellular and molecular experiments and population studies. Thus, we may intend to find new molecular intervention targets for prevention and treatment of restenosis.