Work

E2F5 Accelerates Vascular Smooth Muscle Cells Phenotype Switching in Diabetic Atherosclerosis through Activating Wnt/β-Catenin Pathway

Year: 2025

Type: article

Abstract: BACKGRUOUND: We determined the precise function of E2F transcription factor 5 (E2F5) on the development of diabetic atherosclerosis (DAS) and the underlying mechanisms. METHODS: Apolipoprotein E-knockout mice were intraperitoneally injected with streptozotocin for 5 days and fed a high-fat diet for 12 weeks for establishing an in vivo DAS model. To establish a DAS vascular smooth muscle cells (VSMCs) model, VSMCs were stimulated with fresh medium containing glucose and oxidized low-density lipoprotein. After the final treatment, serum lipids were detected, and aorta tissues were collected for hematoxylin and eosin staining, Western blot, Oil red O staining, and quantitative reverse transcription polymerase chain reaction. The effect of E2F5 on the proliferation, migration, cell cycle, phenotype switching, and cell cycle-related markers of VSMCs were evaluated. RESULTS: In vivo, the expression of E2F5 was elevated in aortic tissues of DAS mice. The downregulation of E2F5 alleviated the symptoms of DAS in mice. Moreover, E2F5 downregulation inhibited the phenotypic transformation of VSMCs in DAS mice. In vitro, the knockdown of E2F5 inhibited the phenotypic transformation of VSMCs. CyclinE overexpression reversed the inhibitory effect of E2F5 silencing on phenotypic transformation of VSMCs. Additionally, we also found that the treatment of BML-284 significantly attenuated the inhibitory effect of E2F5 silencing on phenotypic transformation of VSMCs. CONCLUSION: E2F5 is an injurious factor in the pathogenesis of DAS, and the downregulation of E2F5 could repress VSMCs phenotype switching through inactivating Wnt/β-catenin pathway, and ultimately inhibit the progression of DAS.

Source: Diabetes & Metabolism Journal

DOI: 10.4093/dmj.2024.0588

Authors: Mingxue Di, Jie Wang, Lin Sun, Guang Yang, Qun Xu

Institutions: Shandong Provincial QianFoShan Hospital, Shandong First Medical University, Weifang Medical University

Language: English

Topic: Atherosclerosis and Cardiovascular Diseases

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $500