Effects of microRNA-330 on vulnerable atherosclerotic plaques formation and vascular endothelial cell proliferation through the WNT signaling pathway in acute coronary syndrome

microRNA-330通过WNT信号通路对急性冠脉综合征易损动脉粥样硬化斑块形成及血管内皮细胞增殖的影响

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作者:Jing Ren, Rui Ma, Zhu-Bo Zhang, Yang Li, Ping Lei, Jian-Long Men

Abstract

This study is designed to investigate the effects of microRNA (miR)-330 on atherosclerotic plaques formation and vascular endothelial (VE) cell proliferation by targeting MAPK8 through the WNT signaling pathway in rats with acute coronary syndrome (ACS). Expression of hemodynamic variables were tested. Rats were allocated into control, blank, negative control (NC), miR-330 mimic, miR-330 inhibitor, DDK-1, miR-330 inhibitor + DDK-1 groups. ELISA was used to evaluate the expression of TC, TG, LDL-C, hs-CRP, IL-6, IL-10, TNF-α, and SAA. Immunohistochemistry, reverse transcription quantitative polymerase chain reaction and Western blotting were used for expression of VEGF, MAPK8, WNT1, β-catenin, GSK-3β, p-GSK-3β, CyclinD1, MMP-9, IL-6, and IL-8. MTT assay and flow cytometry for cell proliferation and apoptosis. Compared with the control group, other groups had lower levels of SBP, DBP, MBP, LVSP, and miR-330, higher levels of HR, LVEDP, TC, TG, LDC-C, hs-CRP, IL-6, IL-10, TNF-α, SAA, higher positive protein expression rates of MAPK8, VEGF, and MMP-9, elevated WNT1, β-catenin, GSK-3β and CyclinD1, and reduced cell proliferation. MAPK8-3'-UTR was targeted by miR-330. Compared with the blank group, the miR-330 mimic and DDK-1 groups had higher levels of SBP, DBP, MBP, LVSP, lower levels of HR, LVEDP, TC, TG, LDC-C, hs-CRP, IL-6, TNF-α, SAA, elevated IL-10, decreased positive protein expression rates of MAPK8 and VEGF, raised cell proliferation and reduced cell apoptosis rates. We conclude that overexpressed miR-330 suppresses atherosclerotic plaques formation while promotes VE cell proliferation by targeting MAPK8 through the WNT signaling pathway in ACS rats.

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