An alternative splicing variant of mineralocorticoid receptor discovered in preeclampsia tissues and its effect on endothelial dysfunction

The pathophysiology of preeclampsia (PE) remains unclear. PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern. We collected placental and umbilical artery samples from nor-motensive and PE pregnancies. Mineralocorticoid receptor (MR...

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Bibliographic Details
Published in:Science China. Life sciences 2020-03, Vol.63 (3), p.388-400
Main Authors: Guo, Mengxi, Zhou, Chengliang, Xu, Gufeng, Tang, Lin, Ruan, Yechun, Yu, Ying, Lin, Xianhua, Wu, Dandan, Chen, Hao, Yu, Priscilla, Jin, Luyang, Wang, Yinyu, Wu, Yimei, Ullah, Kamran, Rahman, Tanzil Ur, Liu, Xinmei, Sheng, Jianzhong, Chan, Hsiao-Chang, Huang, Hefeng
Format: Article
Language:English
Subjects:
Aldosterone
Alternative splicing
Biomedical and Life Sciences
Blood pressure
Cardiovascular diseases
Cell proliferation
Endothelial cells
Life Sciences
Offspring
Placenta
Pre-eclampsia
Preeclampsia
Research Paper
Veins & arteries
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Summary:The pathophysiology of preeclampsia (PE) remains unclear. PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern. We collected placental and umbilical artery samples from nor-motensive and PE pregnancies. Mineralocorticoid receptor (MR) and its alternative splicing variant (ASV) expression and their biological effects on PE were examined. An MR ASV was found to be highly expressed in all PE samples and slightly expressed in about half of the normotensive samples (umbilical artery, ~57.58%; placenta, ~36.84%). The MR ASV expression was positively associated with blood pressure in both groups. The MR ASV protein changed the aldosterone-induced expression pattern of MR target genes related to ion exchanges and cell signaling pathways. The MR ASV can also impair the proliferation, migration, and tube formation ability of endothelial cells. These findings indicate that MR ASV in PE placenta plays a pathogenic role in PE pathophysiology, especially in endothelial dysfunction, and the existence of the MR ASV in PE umbilical artery provides a new direction in the study of PE offspring with increased risk of cardiovascular diseases.
ISSN:1674-7305
1869-1889
DOI:10.1007/s11427-018-9535-9