Endothelial cells derived extracellular vesicles promote diabetic arterial calcification via circ_0008362/miR-1251-5p/Runx2 axial

作者：Xiao Lin, Sen He, Su‐Kang Shan, Feng Xu, Feng Wu, Fu‐Xing‐Zi Li, Ming-Hui Zheng, Li-Min Lei, Jia-Yue Duan, Yun-Yun Wu, Yanlin Wu, Ke-Xin Tang, Rongrong Cui, Bei Huang, Junjie Yang, Xiao‐Bo Liao, Jun Liu, Ling‐Qing Yuan · 发表于：Cardiovascular Diabetology · 年份：2024 · DOI：10.1186/s12933-024-02440-7 · 被引用次数：23 · 研究领域：Extracellular vesicles in disease、Biomarkers in Disease Mechanisms、Circular RNAs in diseases

Arterial calcification, an independent predictor of cardiovascular events, increases morbidity and mortality in patients with diabetes mellitus (DM), but its mechanisms remain unclear. Extracellular vesicles (EVs) play an important role in intercellular communication. The study investigates the role and potential mechanisms of EVs derived from endothelial cells (ECs) in regulating vascular smooth muscle cell (VSMC) calcification under high glucose (HG) condition, with a goal of developing effective prevention and treatment strategies for diabetic arterial calcification. The results showed that EVs derived from HG induced ECs (ECHG-EVs) exhibited a bilayer structure morphology with a mean diameter of 74.08 ± 31.78 nm, expressing EVs markers including CD9, CD63 and TSG101, but not express calnexin. ECHG-EVs was internalized by VSMCs and induced VSMC calcification by increasing Runx2 expression and mineralized nodule formation. The circ_0008362 was enriched in ECHG-EVs, and it can be transmitted to VSMCs to promote VSMC calcification both in vitro and in vivo. Mechanistically, miR-1251-5p might be one of the targets of circ_0008362 and they were co-localization in the cytoplasm of VSMCs. Runx2 was identified as the downstream target of miR-1251-5p, and circ_0008362 acted as a sponge, enhancing Runx2 expression and then promoted VSMC calcification. Besides, circ_0008362 could directly interact with Runx2 to aggravate VSMC calcification. Notably, DiR-labelled ECHG-EVs was detected...