Coronary atherosclerosis (AS) is characterized by the formation of plaque in the vessel wall. The structural and functional changes of vascular smooth muscle cells (VSMCs) can promote plaque formation and induce plaque instability.
To investigate the functions and mechanism of miR-222-5p in VSMCs under the treatment of oxidized low-density lipoprotein (ox-LDL).
miR-222-5p expression in ox-LDL-treated VSMCs and the serum of Apolipoprotein E (ApoE) knockout mice was detected by reverse transcription quantitative polymerase chain reaction. The viability and migration of VSMCs were detected by Cell Counting Kit-8 and Transwell assays. Protein levels of proliferation and migration-related factors were evaluated by western blotting. Luciferase reporter assays were performed to explore the binding between miR-222-5p and retinoblastoma susceptibility protein (RB1) gene in VSMCs. ApoE-knockout mice were infected with the lentivirus inhibiting miR-222-5p expression to explore the effect of miR-222-5p on pathological changes. Hematoxylin and eosin (H&E) staining, trichrome staining, and Oil Red O staining were conducted to determine the necrotic core area and atherosclerotic lesion size in the ascending aorta of ApoE-knockout mice.
With the accumulation of ox-LDL concentration and treatment time, miR-222-5p expression was gradually upregulated in VSMCs. Similarly, miR-222-5p expression was increased in the serum of ApoE-knockout mice. miR-222-5p knockdown inhibited the proliferative and migratory abilities of ox-LDL-treated VSMCs, and the inhibitory effect on cellular behaviors was then significantly reversed by co-knockdown of RB1. RB1 is a downstream target gene of miR-222-5p, and miR-222-5p bound with 3′-untranslated region of RB1 in VSMCs. We further confirmed that miR-222-5p knockdown alleviated pathological changes and inhibited lipid deposition in the serum of ApoE-knockout mice in vivo.
miR-222-5p accelerates the dysfunction of VSMCs and promotes pathological changes and lipid deposition in ApoE-knockout mice by targeting RB1. The study may provide novel therapeutic targets for AS.

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