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

Autor: Ying Yu, Yimei Wu, Gu-Feng Xu, Meng-Xi Guo, Kamran Ullah, Ye Chun Ruan, Lu-Yang Jin, He-Feng Huang, Chengliang Zhou, Jian-Zhong Sheng, Xian-Hua Lin, Yinyu Wang, Hsiao Chang Chan, Priscilla Yu, Xin-Mei Liu, Lin Tang, Hao Chen, Tanzil Ur Rahman, Dan-Dan Wu
Rok vydání: 2019
Předmět:
Adult
0301 basic medicine
Spiral artery
medicine.medical_specialty
DNA
Complementary
animal structures
Placenta
Blood Pressure
Pregnancy Proteins
General Biochemistry
Genetics and Molecular Biology
Preeclampsia
03 medical and health sciences
0302 clinical medicine
Mineralocorticoid receptor
Pre-Eclampsia
Pregnancy
Risk Factors
medicine.artery
Internal medicine
Human Umbilical Vein Endothelial Cells
medicine
Humans
Vascular Diseases
Endothelial dysfunction
Aldosterone
Placenta Growth Factor
General Environmental Science
Tube formation
business.industry
Endothelial Cells
Umbilical artery
medicine.disease
Pathophysiology
Alternative Splicing
Receptors
Mineralocorticoid
030104 developmental biology
Endocrinology
medicine.anatomical_structure
030220 oncology & carcinogenesis
embryonic structures
RNA
Female
General Agricultural and Biological Sciences
business
Zdroj: Science China Life Sciences. 63:388-400
ISSN: 1869-1889
1674-7305
Popis: 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.
Databáze: OpenAIRE
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