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miR-125a-3p aggravates ox-LDL-induced HUVEC injury through BAMBI
1Department of Cardiovascular Surgery, Wuhan Asia General Hospital, Wuhan, Hubei, China.
Abstract:
Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of atherosclerotic plaque in the intima of arteries. Among the known regulators of atherosclerosis, microRNAs (miRNAs) have been reported to play critical roles in lipoprotein homeostasis and plaque formation. But the roles of microRNA-125a-3p (miR-125a-3p) in the pathogenesis of AS remain unknown. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to construct the vascular injury model of AS pathogenesis in vitro. miR-125a-3p and BMP and activin membrane-bound inhibitor (BAMBI) expression levels in HUVECs were then measured by quantitative real-time polymerase chain reaction and western blot. The viability and apoptosis of HUVECs were analyzed by Cell Counting Kit-8 assay, TUNEL assay, and flow cytometry, respectively. The relationship between BAMBI 3'-untranslated region and miR-125a-3p was validated by dual luciferase reporter gene assay. miR-125a-3p expression was raised in HUVECs induced with ox-LDL. In HUVECs, miR-125a-3p enhanced the effects of ox-LDL treatment on repressing the viability and promoting the apoptosis of cells. Additionally, BAMBI was confirmed as a direct target of miR-125a-3p and BAMBI overexpression reversed the effects of miR-125a-3p on HUVECs. miR-125a-3p aggravates the dysfunction of HUVECs induced by ox-LDL via BAMBI, which implies that miR-125a-3p is involved in the pathogenesis of AS.
Insights
MicroRNA-125a-3p (miR-125a-3p) exacerbates vascular dysfunction in atherosclerosis by targeting BAMBI. This microRNA promotes cell damage and apoptosis in human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL).
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Pathology
Background:
- Atherosclerosis (AS) is a chronic inflammatory arterial disease.
- MicroRNAs (miRNAs) are key regulators of lipoprotein homeostasis and plaque formation in AS.
- The specific role of microRNA-125a-3p (miR-125a-3p) in AS pathogenesis is currently unknown.
Purpose of the Study:
- To investigate the role and mechanism of miR-125a-3p in the pathogenesis of atherosclerosis.
- To examine the effect of miR-125a-3p on human umbilical vein endothelial cells (HUVECs) under oxidized low-density lipoprotein (ox-LDL) stimulation.
Main Methods:
- Established an in vitro AS model using HUVECs treated with ox-LDL.
- Quantified miR-125a-3p and BAMBI expression using qRT-PCR and Western blot.
- Assessed HUVEC viability, apoptosis, and the miR-125a-3p/BAMBI interaction via CCK-8, TUNEL, flow cytometry, and dual-luciferase assays.
Main Results:
- miR-125a-3p expression was significantly upregulated in ox-LDL-treated HUVECs.
- miR-125a-3p potentiated ox-LDL-induced reduction in HUVEC viability and increased apoptosis.
- BAMBI was identified as a direct target of miR-125a-3p, and its overexpression counteracted miR-125a-3p's effects.
Conclusions:
- miR-125a-3p aggravates ox-LDL-induced HUVEC dysfunction by targeting BAMBI.
- miR-125a-3p plays a significant role in the pathogenesis of atherosclerosis.
- Targeting miR-125a-3p may offer a therapeutic strategy for AS.
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