Shah Amin, Matsumura Nobutoshi, Quon Anita, Morton Jude S, Dyck Jason R B, Davidge Sandra T
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
Clin Sci (Lond). 2017 Aug 10;131(17):2303-2317. doi: 10.1042/CS20171122. Print 2017 Sep 1.
Intrauterine growth restriction (IUGR) following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease (CVD) in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring, which experienced normoxia (21% O) or hypoxia (11% O) underwent sham or MI surgery at 12 weeks of age. Echocardiographic data revealed that both sexes had systolic dysfunction following MI surgery, independent of prenatal hypoxia. Male offspring exposed to prenatal hypoxia, however, had left ventricular dilatation, global dysfunction, and signs of diastolic dysfunction following MI surgery as evident by increased left ventricular internal diameter (LVID) during diastole (MI effect, <0.01), Tei index (MI effect, <0.001), and E/E' ratio (prenatal hypoxia or MI effect, <0.01). In contrast, diastolic dysfunction in female offspring was not as evident. Cardiac superoxide levels increased only in prenatal hypoxia exposed male offspring. Cardiac sarcoendoplasmic reticulum Ca-ATPase2a (SERCA2a) levels, a marker of cardiac injury and dysfunction, decreased in both male and female MI groups independent of prenatal hypoxia. Prenatal hypoxia increased cardiac ryanodine receptor 2 (RYR2) protein levels, while MI reduced RYR2 in only male offspring. In conclusion, male offspring exposed to prenatal hypoxia had an increased susceptibility to ischemic myocardial injury involving cardiac phenotypes similar to heart failure involving diastolic dysfunction in adult life compared with both offspring from healthy pregnancies and their female counterparts.
产前缺氧暴露后的宫内生长受限（IUGR）会导致成年后发生心血管疾病（CVD）的风险更高。我们的目的是评估产前缺氧成年大鼠后代急性心肌梗死（MI）后的心脏易感性及其病理生理机制。经历常氧（21% O）或缺氧（11% O）的雄性和雌性大鼠后代在12周龄时接受假手术或MI手术。超声心动图数据显示，MI手术后两性均出现收缩功能障碍，与产前缺氧无关。然而，产前缺氧的雄性后代在MI手术后出现左心室扩张、整体功能障碍和舒张功能障碍的迹象，舒张期左心室内径（LVID）增加（MI效应，<0.01）、Tei指数（MI效应，<0.001）和E/E'比值（产前缺氧或MI效应，<0.01）可明显看出。相比之下，雌性后代的舒张功能障碍不那么明显。仅在产前缺氧的雄性后代中，心脏超氧化物水平升高。心脏肌浆网Ca-ATP酶2a（SERCA2a）水平是心脏损伤和功能障碍的标志物，在男性和女性MI组中均降低，与产前缺氧无关。产前缺氧会增加心脏雷诺丁受体2（RYR2）蛋白水平，而MI仅降低雄性后代的RYR2水平。总之，与健康妊娠后代及其雌性对应物相比，产前缺氧的雄性后代对缺血性心肌损伤的易感性增加，涉及成年期类似于舒张功能障碍性心力衰竭的心脏表型。
