Long-term exposure to high altitude hypoxia during pregnancy increases fetal heart susceptibility to ischemia/reperfusion injury and cardiac dysfunction.
Long-term exposure to high altitude hypoxia during pregnancy increases fetal heart susceptibility to ischemia/reperfusion injury and cardiac dysfunction.
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DOI：
10.1016/j.ijcard.2018.07.046
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发表时间：
2019-01-01
影响因子：
3.5
通讯作者：
Xiao D
中科院分区：
文献类型：
--
作者：
Zhang P;Ke J;Li Y;Huang L;Chen Z;Huang X;Zhang L;Xiao D
高原缺氧（HAH）暴露影响胎儿发育。然而，胎儿对HAH的心血管反应还不清楚。我们已经验证了这一假设，即长期HAH暴露改变了缺氧/缺血敏感基因的表达，导致胎儿心脏对缺血/再灌注（I/R）损伤和心功能障碍的易感性增加。定时妊娠绵羊暴露于高海拔（3820 m）或保持在海平面（~300 m）110天。从近足月母羊中分离胎心，并在Langendorff制备中进行I/R。HAH降低了雌性胎仔的体重和心脏重量，但对雄性胎仔无影响。与常氧组相比，HAH对基线时左心室（LV）功能没有影响，但增加了LV梗死面积，并减弱了雄性和雌性胎儿缺血后LV功能的恢复。HAH可增加缺氧诱导因子（HIF）-1α和DNA甲基转移酶3b（DNMT 3b）的蛋白水平，但降低蛋白激酶C ε（PKCε）的水平。AHA诱导雄性中miR-210增加4.3倍，雌性心脏中增加2.9倍。此外，HAH对mTOR蛋白和磷酸化水平没有影响，但增加了胎儿心脏中的自噬生物标志物、LC 3B-II蛋白水平和LC 3B-II/LC 3B-I比率。结果表明，妊娠期HAH暴露诱导宫内编程的缺氧/缺血敏感的基因表达模式在发育中的心脏和增加心脏I/R损伤的易感性。
High altitude hypoxia (HAH) exposure affects fetal development. However, the fetal cardiovascular responses to the HAH are not well understood. We have tested the hypothesis that long-term HAH exposure alters the hypoxia/ischemia-sensitive gene expressions, leading to an increase in fetal heart susceptibility to ischemia/reperfusion (I/R) injury and cardiac dysfunction. Time-dated pregnant sheep were exposed to high-altitude (3820 m) or were maintained at sea level (~300 m) for 110 days. Fetal hearts were isolated from the near-term ewes and subjected to I/R in a Langendorff preparation. HAH decreased the fetal body and heart weights in the female but not male fetuses. HAH had no effect on the left ventricle (LV) function at baseline, but increased the LV infarct size and attenuated the post-ischemic recovery of LV function in both male and female fetuses, as compared with the normoxic groups. HAH increased the protein levels of hypoxia-inducible factor (HIF)-1α and DNA methyltransferases type 3b (DNMT3b), but attenuated protein kinase C epsilon (PKCε) levels in the fetal hearts. AHA induced a 4.3 fold increase of miR-210 in the males and a 2.9 fold increase in female hearts. In addition, HAH had no effect on mTOR protein and phosphorylation levels but increased the autophagy biomarker, LC3B-II protein levels and LC3B-II/LC3B-I ratio in the fetal hearts. The results suggest that gestational HAH exposure induces in utero programming of the hypoxia/ischemia-sensitive gene expression pattern in the developing heart and increases cardiac susceptibility to I/R injury.
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影响因子：
8.3
作者：
Hu, Xiang-Qun;Dasgupta, Chiranjib;Zhang, Lubo
通讯作者：
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DOI：
10.1016/j.bbamcr.2014.06.012
发表时间：
2014-11
影响因子：
5.1
作者：
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