The EGR3 gene modulates CRP and VCAM-1 expression to promote the development of atherosclerosis

This study was designed to explore early growth response factor 3(EGR3) expression in atherosclerosis models and investigate the molecular mechanism.

Human coronary artery endothelial cells (HCAECs) were cultured and treated with oxidized low-density lipoprotein (ox-LDL) to establish an atherosclerosis model in vitro. Moreover, an in vivo atherosclerosis model was established by tail vein injection of AAV8-PCSK9 virus into mice who were then fed a high-fat diet. EGR3 expression was manipulated through cellular lentiviral transfection and conditional gene knockout in mice. Oil red O staining was used to assess lipid droplet and mouse aortic plaque formation. HE staining was used to observe pathological changes in mouse aortic tissue. To quantify C-reactive protein (CRP) levels, ELISA was conducted on HCAEC lysates and mouse serum samples. Western blot analysis was conducted to determine EGR3 and vascular cell adhesion molecule-1 (VCAM-1) protein levels and in both cellular lysates and mouse aortic tissue.

In vitro and in vivo studies revealed that EGR3 expression was elevated in the ox-LDL group. Furthermore, in vitro studies revealed that the CRP and VCAM-1 expression levels were significantly reduced and that lipid droplet formation was inhibited by EGR3 inhibition. Consistently, CRP, VCAM-1, blood glucose and lipid levels, and the severity of atherosclerotic lesions in mice were significantly reduced in Egr3 knockout mice.

Our findings indicate that atherosclerosis development appears to be associated with the regulation of CRP and VCAM expression by EGR3. These results suggest that targeting EGR3 may be a promising approach for treating atherosclerosis.