MicroRNA-325 facilitates atherosclerosis progression by mediating the SREBF1/LXR axis via KDM1A
Life Sciences(2021)
摘要
Aims: MicroRNA-325 (miR-325) was significantly upregulated in diabetic atherosclerosis, while its specific role in atherosclerosis has not been established. The present study was set to probe the effects of miR-325 on the atherosclerosis progression and to explore the mechanisms. Materials and methods: The ApoE(-/-) mouse with atherosclerosis was developed to detect the miR-325 expression in atherosclerotic plaques. The pathological symptoms of atherosclerotic mice were observed by injection of miR-325 mimic or inhibitor. Subsequently, the levels of CRP, IL-6, IL-1 beta and TNF-alpha in mouse serum were measured by ELISA. Then, miR-325 was overexpressed or silenced in RAW264.7-derived foam cells (FCs), and cholesterol efflux and lipid content were evaluated. Furthermore, miR-325 expression was altered in HA-VSMCs to measure viability and apoptosis. The targets of miR-325 were predicted in a bioinformatics website, and the expression of KDM1A, SREBF1 and PPAR gamma-LXR-ABCA1 in mouse arterial tissues and cells was detected, followed by rescue experiments. Key findings: miR-325 was elevated in arterial tissues of atherosclerotic mice, and miR-325 inhibition in mice reduced the contents of total cholesterol, triglyceride, low-density lipoprotein, and CRP, IL-6, IL-1 beta and TNF-alpha levels in mouse serum. miR-325 inhibitor facilitated the cholesterol efflux and decreased the lipid content in RAW264.7 cells, and also diminished HA-VSMC viability. miR-325 targeted KDM1A to reduce SREBF1 expression, and further KDM1A suppression inhibited cholesterol efflux in RAW264.7 cells and the activation of PPAR gamma-LXR-ABCA1 pathway. Significance: miR-325 lowers SREBF1 expression by decreasing KDM1A expression, thereby inhibiting the activation of the PPAR gamma-LXR-ABCA1 pathway and thus promoting atherosclerosis.
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关键词
Atherosclerosis,microRNA-325,KDM1A,SREBF1,PPAR gamma-LXR-ABCA1 axis
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