近期多项研究证实孕期不良因素诱导胎儿肾素-血管紧张素系统 (RAS) 的发育改变可致出生后患心血管疾病的危险性增加，其中表观遗传调控已被认为是孕期不良因素导致胎源性心血管疾病发生的重要机制，同时孕期不良因素所致胎儿发育障碍与宫内缺血缺氧密切相关。我们预实验结果显示孕期缺氧的子代大鼠易患高血压，同时缺氧也改变了血管内皮细胞中RAS的表达。然而，迄今有关孕期缺氧诱导子代高血压发生的机理知之甚少，有待进一步探讨。因此，我们提出假说：孕期缺氧可能通过诱导RAS表观遗传修饰改变导致子代血管功能、血压调节障碍。为了验证这一假说，我们建立孕鼠及细胞缺氧模型，运用Real-time PCR及甲基化敏感性PCR等实验方法，从分子、细胞、组织及动物整体水平上探讨孕期缺氧导致子代高血压 “程序化”发生的分子机理。本研究成果也将有利于增加对RAS通路调控的新认识，为早期干预心血管性疾病提供新思路。

Recent progress has demonstrated that a variety of adverse factors during pregnancy leading to developmental changes in renin-angiotensin system (RAS), which is linked to cardiovascular diseases in later life. Meanwhile, it has been accepted that the changes in RAS epigenetic modifications are important molecular mechanisms in developmental “programming” of cardiovascular diseases. In fact, a number of adverse intrauterine factors induced abnormal fetal development that could be related to in utero hypoxia. Our preliminary experimental results show that prenatal hypoxia was predisposed to high blood pressure in the offspring rats. However, the underlying "programming" mechanism involved in prenatal hypoxia-induced offspring hypertension is still poorly understood. Meanwhile, we found that hypoxia of vascular endothelial cell indeed changed the expression of RAS in our preliminary experimental results. Therefore, this project will determine the relationship between prenatal hypoxia-induced changes of RAS epigenetic modifications and blood pressure dysregulation in fetal origins. We have established the prenatal hypoxia and cell models. This project will use Real-time PCR, and methylation sensitive PCR method, at the molecules, cells, tissues and in vivo levels to investigate the molecular mechanism on prenatal hypoxia-induced blood pressure dysregulation in fetal origins. This proposed project will provide new information that will contribute to further understanding RAS pathway, as well as adding new information on early prevention of cardiovascular diseases in fetal origins.