血管平滑肌表型转化发生在诸多心血管疾病发生的早期。寻找内源性的维持血管平滑肌细胞收缩表型的分子和机制有助于防止再狭窄、动脉粥样硬化等疾病发生。prohibitin2（PHB2）是维持线粒体稳态的关键分子，其在平滑肌细胞中尚无研究。我们的预实验结果发现PHB2维持血管平滑肌细胞收缩表型、上调线粒体氧化磷酸化水平；增强线粒体氧化磷酸化能够逆转PHB2缺失引起的平滑肌细胞去分化。因此我们提出假说：PHB2通过调节线粒体氧化磷酸化维持血管平滑肌细胞收缩表型。在本项目中，我们将利用平滑肌细胞PHB2诱导敲除小鼠明确PHB2在平滑肌细胞表型调控及相关疾病中的作用；阐明PHB2通过维持线粒体氧化磷酸化影响平滑肌表型及相关疾病发展；寻找PHB2维持平滑肌表型中的关键分子，为再狭窄、动脉粥样硬化等疾病的临床预防提供新靶点。

Vascular smooth muscle cells (VSMCs) are highly phenotypically plastic, and loss of the contractile phenotype in VSMCs has been recognized at the early onset of the pathology of a variety of vascular diseases, such as post-injury restenosis and atherosclerosis. However, the endogenous regulatory mechanism to maintain contractile phenotype in VSMCs remains elusive. Prohibitin2 is a key molecule that maintaining the homeostasis of mitochondria. The role of prohibitin2 in VSMCs and vascular biology is still in the mist. We firstly found prohibitin2 deficiency promoted VSMC phenotypic transition as well as impaired mitochondrial oxidative phosphorylation (OXPHOS) activity. However, enhancement of OXPHOS rescued VSMC dedifferentiation upon prohibitin2 deficiency. Thus we hypothesized prohibitin2 maintains VSMC contractile phenotype via upregulating mitochondrial OXPHOS. As we plan, we will confirm the role of prohibitin2 in post-injury restenosis and atherosclerosis mouse models and VSMC specific tamoxifen induced prohibitin2 knockout mice. Then we will observe the role of mitochondrial OXPHOS on the regulation of VSMC phenotype by prohibitin2 both in vitro and in vivo. Further we will explore the possible interacting proteins of prohibitin2 in regulating VSMC phenotype. Through this project, we expect to clarify the role of prohibitin2 in VSMC phenotypic modulation and the underlying mechanisms. Our project will provide a new target for clinical prevention and treatment of vascular diseases such as post-injury restenosis and atherosclerosis.