Manli Zhang1, Manna Zhang2, Wenli Wang3, Hui Chen1, Xia Wang1, Kun Zhao1, Ze Li1, Jiangqing Xu1, Fei Tong1. 1. Department of Critical Care Medicine, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei, China. 2. Department of Clinical Laboratory, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei, China. 3. Department of Obstetrics, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei, China.
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. AJTR
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. AJTR
Authors: Maro R I Williams; Shanhong Ling; Tye Dawood; Kazuhiko Hashimura; Aozhi Dai; He Li; Jun-Ping Liu; John W Funder; Krishnankutty Sudhir; Paul A Komesaroff Journal: J Clin Endocrinol Metab Date: 2002-01 Impact factor: 5.958
Authors: Shawn L Straszewski-Chavez; Irene P Visintin; Natasha Karassina; Georgyi Los; Peter Liston; Ruth Halaban; Ahmed Fadiel; Gil Mor Journal: J Biol Chem Date: 2007-02-28 Impact factor: 5.157