# The miR-2110/TRAF3 axis is associated with endothelial dysfunction and atherosclerosis in coronary heart disease

## TL;DR

This study shows that reduced miR-2110 levels in coronary heart disease lead to endothelial dysfunction by targeting TRAF3, which may contribute to atherosclerosis and inflammation.

## Contribution

The study identifies TRAF3 as a direct target of miR-2110 and reveals a novel regulatory pathway in coronary heart disease.

## Key findings

- miR-2110 is significantly downregulated in coronary heart disease patients.
- TRAF3 is confirmed as a direct target of miR-2110 and is upregulated in CHD patients and atherosclerotic lesions.
- miR-2110 overexpression in endothelial cells causes impaired proliferation, migration, and increased senescence.

## Abstract

Coronary heart disease (CHD) is driven by endothelial dysfunction and chronic vascular inflammation. hsa-miR-2110 (miR-2110) has been associated with adverse cardiovascular outcomes, but its mechanistic role in CHD remains unclear. In this study, miR-2110 expression was quantified in peripheral blood from CHD patients and healthy controls. Functional effects were assessed in EA.hy926 endothelial cells following lentiviral overexpression of miR-2110. The target gene TRAF3 was identified by RNA sequencing, bioinformatic analysis, and validated by dual-luciferase reporter assays, RT-qPCR, and Western blotting. TRAF3 expression was further evaluated in CHD patient blood samples and in atherosclerotic lesions from ApoE−/− mice fed a high-fat diet. miR-2110 was significantly downregulated in CHD patients. Overexpression of miR-2110 in endothelial cells impaired proliferation and migration, induced S-phase arrest, reduced apoptosis, and promoted cellular senescence. TRAF3 was confirmed as a direct target of miR-2110. TRAF3 was significantly upregulated in CHD patients. In ApoE−/− mice, TRAF3 protein expression was increased in atherosclerotic lesions, predominantly within the tunica intima. Pathway enrichment predicted NF-κB–related signaling among the enriched pathways potentially associated with the miR-2110/TRAF3 axis. Together, our findings suggest that the miR-2110/TRAF3 axis represents a novel regulatory pathway involved in CHD, potentially relevant to endothelial dysfunction and inflammatory signaling.

Image 1

•miR-2110 is downregulated in coronary heart disease and is associated with endothelial dysfunction.•TRAF3 is identified as a direct target of miR-2110 in endothelial cells.•Dysregulated miR-2110/TRAF3 expression is observed in coronary heart disease.

miR-2110 is downregulated in coronary heart disease and is associated with endothelial dysfunction.

TRAF3 is identified as a direct target of miR-2110 in endothelial cells.

Dysregulated miR-2110/TRAF3 expression is observed in coronary heart disease.