卵巢糖蛋白1通过与MYH9的相互作用诱导血管重塑促进高血压
Congxia Bai1,2, Ming Su3, Yaohua Zhang1,4
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital (C.B., Y.Z., Y.S., L.S., N.X., H.X., H.W., M.Z., J.P., J.L., R.H., H.L., J.C.), National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Circulation
|September 29, 2022
概括
卵巢糖蛋白1 (OVGP1) 通过DNA低甲基化与高血压有关. OVGP1通过与MYH9相互作用促进血管重塑和功能障碍,确定其为高血压因素.
科学领域:
- 心血管生物学
- 表观遗传学
- 分子医学
背景情况:
- 高血压是一种常见的心血管疾病,其机制不明,受遗传和环境因素的影响.
- DNA甲基化是一种表观遗传修饰,它将环境影响与基因表达联系起来,这对理解高血压至关重要.
- 对高血压患者的差异性DNA甲基化查对于阐明疾病机制至关重要.
研究的目的:
- 研究DNA甲基化在高血压中的作用.
- 确定参与高血压发展的特定基因和分子途径.
- 探索OVGP1在血压调节和血管重塑中的功能意义.
主要方法:
- 使用Illumina 450K BeadChip和火烧测序进行全基因组甲基化选.
- 与酶相关的免疫吸收试验 (ELISA) 检测血OVGP1水平.
- 产生和分析Ovgp1转基因和淘汰小鼠,包括血压测量和血管研究.
- 蛋白与蛋白相互作用测定 (拉向,质谱,共免疫沉) 以确定OVGP1的相互作用伙伴.
主要成果:
- 在高血压患者中,OVGP1促进体中的低甲基位 (cg20823859) 与OVGP1度的增加有关.
- 在小鼠中,OVGP1过度表达导致血压升高,血管功能障碍,重塑,氧化应激和炎症.
- OVGP1 缺乏可以缓解血管血管因子的损伤.
- 发现OVGP1与MYH9相互作用,MYH9的抑制降低了OVGP1引起的高血压和血管重塑.
结论:
- 低甲基化OVGP1促进剂对OVGP1进行上调,从而导致高血压.
- 通过与MYH9的相互作用促进血管重塑和功能障碍,OVGP1起到预防高血压的作用.
- 针对OVGP1- MYH9相互作用可能为高血压提供治疗策略.
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