Dehydroepiandrosterone inhibits vascular proliferation and inflammation by modulating the miR-486a-3p/NLRP3 axis.
Year: 2022
Type: article
Abstract: OBJECTIVES: In vascular remodeling diseases, proliferation and inflammation of vascular smooth muscle cells (VSMCs) constitute the basic pathologic processes. Dehydroepiandrosterone (DHEA) exerts a protective effect on the cardiovascular system, but the molecular mechanism is unclear. METHODS: The plasma DHEA was measured using enzyme-linked immunosorbent assay (ELISA) kits. The neointima hyperplasia was assessed by hematoxylin/eosin staining. MiRNA microarray analysis was used to compare the influence of Ang II and DHEA on miRNA expression profiles in VSMCs. Cell counting and MTS assay were used to evaluate the effect of Ang II, DHEA and miR-486a-3p on VSMCs proliferation. qRT-PCR was performed to detect the expression of miR-486a-3p, PCNA, IL-1β and NLRP3. Western blot analysis was performed to detect the expressions of PCNA, IL-1β and NLRP3 after miR-486a-3p was knocked down or overexpressed in VSMCs. RESULTS: DHEA suppressed neointimal and VSMCs proliferation and inflammation. Using miRNA microarray analysis, we found that DHEA upregulated the expression of miR-486a-3p in VSMCs. Further experiments indicated that DHEA promoted miR-486a-3p expression in VSMCs and in the vascular intima. Gain- and loss-of-function experiments revealed that transfection of miR-486a-3p mimic inhibited proliferation and inflammation of VSMCs, which improved intimal hyperplasia. On the contrary, deletion of miR-486a-3p promoted VSMCs proliferation and inflammation. Furthermore, DHEA suppressed NOD-like receptor family pyrin domain containing 3 (NLRP3) expression and reduced VSMCs proliferation and inflammation. Importantly, DHEA inhibited NLRP3 expression via miR-486a-3p in VSMCs. CONCLUSIONS: DHEA inhibited VSMCs and vascular intimal proliferation and inflammation by regulating the miR-486a-3p/NLRP3 axis. Therefore, DHEA might be a candidate cardiovascular protective agent in the future.
Source: PubMed
Authors: Manli Zhang, Manna Zhang, Wenli Wang, Hui Chen, Xia Wang, Kun Zhao, Ze Li, Jiangqing Xu, Fei Tong
Institution: Second Hospital of Hebei Medical University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4306669193