Abstract
We explore miR‐150‐5p in atherosclerosis (AS). The AS model was constructed using Apo E−/− mice with an injection of the miR-150-5p mimic or an inhibitor. Pathological characteristics were assessed using Oil red O staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expressions of microRNA-150-5p (miR-150-5p), STAT1, α-SMA (α-smooth muscle actin) and proliferating cell nuclear antigen (PCNA). Targetscan and dual-luciferase reporter assay were used to analyze the interaction between miR-150-5p and STAT1. The viability, migration, cell cycle and α-SMA and PCNA expressions in oxidized low-density lipoprotein (ox-LDL)-stimulated primary human aortic smooth muscle cells (ASMCs) were assessed using molecular experiments. miR-150-5p was reduced in both AS mice and ox-LDL-stimulated human aortic smooth muscle cells but STAT1 had the opposite effect. The miR‐150‐5p inhibitor alleviated the increase of lipid plaque and reduced collagen accumulation in the aortas during AS. Upregulation of α-SMA and PCNA was reversed by miR-150-5p upregulation. STAT1 was targeted by miR‐150‐5p, and overexpressed miR-150-5p weakened the ox-LDL-induced increase of viability and migration abilities and blocked cell cycle in ASMCs, but overexpressed STAT1 blocked the effect of the miR‐150‐5p mimic. This paper demonstrates that miR-150-5p has potential as a therapeutic target in AS, with plaque stabilization by regulating ASMC proliferation and migration via STAT1.
Highlights
We found that miR-150-5p was reduced in both AS mice and human aortic smooth muscle cells (HASMCs) stimulated by ox‐LDL, a well‐documented risk contributor for AS, but STAT1 had an opposite pattern. miR-150-5p downregulation promoted plaque stabilization via increased smooth muscle cells and collagen content and decreased lipid accumulation in the aortas during AS
In vitro functional studies showed that overexpressed miR-150-5p attenuated the oxidized low-density lipoprotein (ox-LDL)-induced increase in proliferation and migration of HASMCs by targeting STAT1
Our findings showed the potential role of miR-150-5p in regulating atherosclerotic plaque stability and in regulating proliferation and migration in the ox‐LDL‐stimulated cellular model of AS via targeting STAT1
Summary
Abstract: We explore miR‐150‐5p in atherosclerosis (AS). The AS model was constructed using Apo E−/− mice with an injection of the miR-150-5p mimic or an inhibitor. MiR-150-5p was reduced in both AS mice and ox-LDL-stimulated human aortic smooth muscle cells but STAT1 had the opposite effect. This paper demonstrates that miR-150-5p has potential as a therapeutic target in AS, with plaque stabilization by regulating ASMC proliferation and migration via STAT1. Recent research indicates that lncRNA TNK2‐AS1 inhibits proliferation and migration of oxidized low-density lipoprotein (ox-LDL)-stimulated human aortic smooth muscle cells (HASMCs) [22]. The mice in the Model + M group were injected with 5 × 108 TU/mL lentivirus suspension (20 μL) containing the miR-150-5p mimic (5′-UCUCCCAACCC UUGUACCAGUG-3′) via the tail vein. The mice in the Model + I group were injected with 5 × 108 TU/mL lentivirus suspension containing the miR-150-5p inhibitor (20 μL, 5′-CACUGG UACAAGGGUUGGGAGA-3′) via the tail vein. All sequences were purchased from Hanheng Biotechnology (Hanheng Biotechnology Co., Ltd., Shanghai, China)
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