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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
A dysregulated microRNA-26a/EphA2 axis impairs endothelial progenitor cell function via the p38 MAPK/VEGF pathway
Keqiang Zuo1, Kangkang Zhi, Xiaoping Zhang
1Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Background:
Dysfunction of circulating endothelial progenitor cells (EPCs) is associated with the onset of cardiovascular disorders. Circulating microRNAs (miRNAs) have been recognized as novel biomarkers and potential therapeutic targets. Here, we examined the role of miR-26a overexpression in atherosclerosis and explored the underlying mechanisms.
Methods:
EPCs were obtained from patients with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2 and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF levels were determined by enzyme linked immunosorbent assay. Cell viability was assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a target of miR-26a.
Results:
MiR-26a was overexpressed in patients with atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown modulated the activity of p38 MAPK and the levels of VEGF in EPCs.
Conclusions:
The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a mechanism involving the p38 MAPK/VEGF pathway.
Insights
MicroRNA-26a (miR-26a) overexpression impairs endothelial progenitor cell function in atherosclerosis by targeting EphA2. This mechanism involves the p38 MAPK/VEGF pathway, offering potential therapeutic insights for cardiovascular disorders.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Biomarker Discovery
Background:
- Endothelial progenitor cell (EPC) dysfunction is linked to cardiovascular disorders.
- MicroRNAs (miRNAs) are emerging as key biomarkers and therapeutic targets.
- This study investigates the role of miR-26a in atherosclerosis.
Purpose of the Study:
- To examine the role of miR-26a overexpression in atherosclerosis.
- To elucidate the underlying molecular mechanisms.
- To identify potential therapeutic targets for cardiovascular disease.
Main Methods:
- EPCs isolated from atherosclerosis patients and healthy controls.
- Hypoxia exposure to mimic atherosclerotic conditions.
- qRT-PCR, western blotting, ELISA, MTT assay, and luciferase assays used to measure miR-26a, EphA2, p38 MAPK, and VEGF levels.
Main Results:
- MiR-26a was overexpressed in atherosclerosis patients, correlating with EPC dysfunction.
- EphA2 identified as a direct target of miR-26a.
- MiR-26a modulated p38 MAPK activity and VEGF levels, impacting EPC function.
Conclusions:
- MiR-26a exacerbates atherosclerosis by targeting EphA2.
- The p38 MAPK/VEGF pathway mediates the effects of miR-26a in EPCs.
- Findings suggest miR-26a as a potential therapeutic target for atherosclerosis.
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