MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression

• DOI: 10.1186/s12933-024-02404-x
• Publication Date: 2024-09-09T15:04:10Z
• Authors: Bei Guo; Tong-Tian Zhuang; Chang-Chun Li; Fuxingzi Li; Su-Kang Shan; Ming-Hui Zheng; Qiu-Shuang Xu; Yi Wang; Li-Min Lei; Ke-Xin Tang; Wenlu Ouyang; Jia-Yue Duan; Yun-Yun Wu; Ye-Chi Cao; Muhammad Hasnain ...; Zhi-Ang Zhou; Xiao Lin; Feng Wu; Feng Xu; Xiao-Bo Liao; Ling-Qing Yuan
• Keywords: Male; Mice, Knockout, ApoE; Myocytes, Smooth Muscle; Aortic Diseases; Adipose tissue; Apoptosis; Exosomes; Muscle, Smooth, Vascular; Cell Movement; Diseases of the circulatory (Cardiovascular) system; Animals; Obesity; Cells, Cultured; Melatonin; Cell Proliferation; Research; Endothelial Cells; Atherosclerosis; Plaque, Atherosclerotic; Mice, Inbred C57BL; MicroRNAs; Disease Models, Animal; RC666-701; Disease Progression; MiR-132/212; Signal Transduction

Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes.The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests.We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX.These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.