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

Mengxi Guo, Chengliang Zhou, Gufeng Xu, Lin Tang, Yechun Ruan, Ying Yu, Xianhua Lin, Dandan Wu, Hao Chen, Priscilla Yu, Luyang Jin, Yinyu Wang, Yimei Wu, Kamran Ullah, Tanzil Ur Rahman, Xinmei Liu, Jianzhong Sheng, Hsiao Chang Chan, Hefeng Huang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

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.

Original languageEnglish
JournalScience China Life Sciences
DOIs
Publication statusAccepted/In press - 1 Jan 2019
Externally publishedYes

Keywords

  • alternative splicing variant
  • endothelial dysfunction
  • mineralocorticoid receptor
  • offspring
  • preeclampsia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

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