期刊
MICROVASCULAR RESEARCH
卷 139, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2021.104236
关键词
KCNQ1OT1; miR-145-5p; Atherosclerosis; Ox-LDL
This study revealed that KCNQ1OT1 expression was upregulated and miR-145-5p was downregulated in atherosclerotic plaques of AS mice and ox-LDL-treated THP-1 cells. Attenuation of lipid metabolic disorders and inflammation was observed in vivo and in vitro by either KCNQ1OT1 knockdown or miR-145-5p overexpression. Furthermore, KCNQ1OT1 acted as a molecular sponge of miR-145-5p, influencing AS progression.
Background: Atherosclerosis (AS) is a lipid-driven inflammatory disease of the arterial intima. Evidence is growing that dysregulation of lncRNAs is implicated in the pathogenesis of AS. In this research, the role of lncRNA KCNQ1OT1 in AS was investigated. Methods: ApoE-/-mice were fed on a high fat diet to establish mouse models of AS. Macrophages (THP-1) were treated with oxidized low-density lipoprotein (ox-LDL) to establish cell models of AS. Atherosclerotic lesions of AS mice were determined by performing Oil red O staining. Lipid metabolic disorders and inflammatory were detected using specific assay kits. KCNQ1OT1 and miR-145-5p expression was measured using RT-qPCR. Levels of PPAR alpha and CPT1 were measured using western blot. Results: KCNQ1OT1 expression was upregulated and miR-145-5p was downregulated in atherosclerotic plaques of AS mice and ox-LDL-treated THP-1 cells. Lipid metabolic disorders and inflammation in vivo and in vitro were attenuated by either KCNQ1OT1 knockdown or miR-145-5p overexpression. Additionally, KCNQ1OT1 acted as a molecular sponge of miR-145-5p and downregulated miR-145-5p expression. Furthermore, silencing miR-145-5p abolished the effect of KCNQ1OT1 knockdown. Conclusion: Silencing KCNQ1OT1 attenuates AS progression by sponging miR-145-5p.
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