高血压性血管重构（HVR）主要表现为血管中膜增生，是高血压靶器官损害及不良预后的独立预测因子。而血管平滑肌细胞（VSMC）表型转换是中膜增生的关键机制。Hippo/YAP通路是高度保守的信号通路，在胚胎血管发育中发挥决定性作用，被PDGF-BB激活后可促VSMC表型转换，但其在HVR中的作用尚不清楚。我们的预实验发现，大鼠HVR模型颈动脉YAP表达明显上调，并表现出VSMC表型转换；公认的促HVR因子血管紧张素II（Ang-II）亦可上调VSMC YAP的表达并促进其向核内聚集（活化）。因此，我们提出科学假说：Hippo/YAP通路被Ang-II激活后，可能通过促进VSMC表型转换，最终诱导HVR形成。本课题拟采用sh-YAP腺病毒转染、免疫共沉淀、基因芯片、双荧光素酶报告系统等技术，通过体内外实验来验证假说并阐述其具体的分子机制。为Hippo/YAP通路做为HVR治疗靶点提供理论依据。

Hypertensive vascular remodeling (HVR), characterized by media hyperplasia, is the independent risk factor of target organ damage and adverse prognosis in hypertension patients. Vascular smooth muscle cell (VSMC) phenotypic modulation is the key mechanism for media hyperplasia. Hippo/YAP pathway is an evolutionarily conserved molecular mechanism, which has been reported to participate in PDGF-BB-induced VSMC phenotypic modulation, and play a fundamental role in fetal vasculogenesis. However, the role of Hippo/YAP in HVR remains elusive. Our previous study demonstrated that the expression of YAP in the carotid artery was elevated in HVR rat model, accompanied with VSMC phenotypic modulation. We also found that in VSMC, Ang-II, the widely-accepted HVR-inducing factor, up-regulated the expression and promoted the nuclear accumulation of YAP. As a result, we hypothesize that, when activated by Ang-II, the Hippo/YAP pathway could induce VSMC phenotypic modulation and lead to HVR formation. This study aims to test this hypothesis and elucidate its molecular mechanism by a series of in vitro and in vivo experiments, such as sh-YAP adenovirus transfection, Co-IP, microarray and dual luciferase reporter assay. Our study will provide theoretical basis for Hippo/YAP pathway as a novel therapeutic target of HVR.