OVGP1在血管重塑中的作用及其致高血压的功能机制研究

鉴定高血压相关新基因十分重要，我们全基因组甲基化差异分析发现OVGP1可能与高血压相关，它能促进血管重塑相关基因TGF-β1表达，并与血管重构相关蛋白FLOT1和E-Cadherin相互作用。据此推测OVGP1可能通过调控TGF-β1或与FLOT1，E-Cadherin相互作用，促进血管重塑从而导致高血压。我们首先利用基因芯片、生物信息学及分子生物学方法分析OVGP1过表达或低表达后血管重塑、血压调节相关基因的表达改变及相关信号通路；利用CoIP，免疫荧光等技术验证分析OVGP1与FLOT1，E-Cadherin相互作用；然后分析OVGP1对血管内皮细胞和平滑肌细胞的增殖、形态、粘附和迁移的影响。最后在整体水平观察OVGP1对血管重塑及血压调节的作用。本研究从表观遗传学研究为切入点，深入探讨相关基因OVGP1的作用机制，有望为表观遗传参与高血压发病提供新证据，为高血压的防治提供新的靶点。

It is crucial to identify novel hypertension-associated genes. Our previous results from Genome-Wide Analysis of DNA Methylation indicated that OVGP1 may be associated with hypertension. OVGP1 promotes the expression of TGF-β1 and interacts with vascular remodeling genes such as FLOT1 and E-Cadherin, which may induce vascular remodeling and thus result in hypertension. Therefore, we speculate that OVGP1 may promote vascular remodeling and hypertension through regulation of TGF-β1 expression and/or interaction with FLOT1 and/or E-Cadherin. To investigate the role of OVGP1 on vascular remodeling and hypertension, the expression of vascular remodeling- and hypertension-associated genes together with related signaling pathways will be measured after OVGP1 overexpression or knockdown by using gene microarray, bioinformatics and molecular biology assays. The interaction among OVGP1, FLOT1 and E-Cadherin will be analyzed by using CoIP and immunofluorescence assays. Then, the effects of OVGP1 on proliferation, morphology, adhesion and migration of both HUVEC and HUASMC will be analyzed. At last, we will observe the effects of OVGP1 on vascular remodeling and blood pressure in vivo. The present study is started from epigenetic evidences and deeply investigates the mechanisms of OVGP1 on vascular remodeling and blood pressure regulation. Therefore, our study may provide novel evidences to epigenetic mechanisms on hypertension, and thus may explore novel therapeutic targets for hypertension.