Long-term exposure to high altitude hypoxia during pregnancy increases fetal heart susceptibility to ischemia/reperfusion injury and cardiac dysfunction

International Journal of Cardiology
Peng ZhangDaliao Xiao

Abstract

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 p...Continue Reading

Citations

Jun 22, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Qi RenChangjie Ren
Jul 9, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Loren P ThompsonGraham W Aberdeen
Aug 13, 2020·International Journal of Molecular Sciences·Jianli HeTianshi Wang
Jun 9, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Li ChenMing Guo

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