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) 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.
Keywordspreeclampsia mineralocorticoid receptor alternative splicing variant offspring endothelial dysfunction
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We thank the patients and the doctors and nurses who assisted with this study and lab colleagues who shared their opinions on this topic. This work was supported by the National Key Research and Development Program of China (2017YFC1001303), International Cooperation Project of China and Canada NSFC (81661128010), National Natural Science Foundation of China (31471405, 81671456, and 81671412), and the National Key Basic Research Program (2013CB967404).
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