1Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Reprod Sci. 2014 Jan;21(1):52-62. doi: 10.1177/1933719113488447. Epub 2013 May 20.
Excess salt intake during pregnancy may alter fetal organ structures and functions leading to increased risks in the development of cardiovascular diseases in later life. The present study determined whether and how the prenatal high-salt (HS) diets affect renin-angiotensin system (RAS) that may mediate cardiac cell death.
Angiotensin II receptors, AT1 and AT2, protein expression was increased in the myocardium of the offspring exposed to prenatal HS; apoptotic cells appeared in the myocardium of the adult offspring. Mitochondrion was isolated in cell experiments, and the data showed cardiomyocyte apoptosis requiring cytochrome C release. Pretreating H9C2 cells with AT2 agonist CGP42112A induced cell apoptosis in DNA fragments and activated caspase 3. CGP42112A increased mitochondrion cytochrome C release and apoptosis in the cells.
Both in vitro and in vivo study demonstrated that cardiomyocyte apoptosis was related to AT2 activation. Prenatal HS diets may reprogram RAS that mediates apoptosis in the offspring myocardium, and AT2 may contribute to cardiomyocyte apoptosis via the cytochrome C release pathway.
孕期盐摄入量过多可能会改变胎儿器官结构和功能，增加其日后罹患心血管疾病的风险。本研究旨在确定孕期高盐（HS）饮食是否以及如何影响肾素-血管紧张素系统（RAS），从而介导心肌细胞死亡。
在接受产前 HS 饮食暴露的后代心肌中，血管紧张素 II 受体 AT1 和 AT2 的蛋白表达增加；成年后代的心肌中出现凋亡细胞。在细胞实验中分离线粒体，数据显示需要细胞色素 C 释放的心肌细胞凋亡。用 AT2 激动剂 CGP42112A 预处理 H9C2 细胞，可诱导细胞凋亡产生 DNA 片段并激活 caspase 3。CGP42112A 增加了线粒体细胞色素 C 的释放和细胞凋亡。
体内外研究均表明，心肌细胞凋亡与 AT2 激活有关。产前 HS 饮食可能会重新编程介导后代心肌细胞凋亡的 RAS，AT2 可能通过细胞色素 C 释放途径促进心肌细胞凋亡。
