| Title | Extracellular vesicles carrying proinflammatory factors may spread atherosclerosis to remote locations |
| Authors | Peng, Mengna Sun, Rui Hong, Ye Wang, Jia Xie, Yi Zhang, Xiaohao Li, Juanji Guo, Hongquan Xu, Pengfei Li, Yunzi Wang, Xiaoke Wan, Ting Zhao, Ying Huang, Feihong Wang, Yuhui Ye, Ruidong Liu, Qian Liu, George Liu, Xinfeng Xu, Gelin |
| Affiliation | Nanjing Univ, Affiliated Jinling Hosp, Dept Neurol, Med Sch, Nanjing 210002, Jiangsu, Peoples R China Second Mil Med Univ, Naval Med Univ, Shanghai Changhai Hosp, Dept Neurol, Shanghai 200433, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Dept Neurol, Nanjing 210002, Jiangsu, Peoples R China Southern Med Univ, Jinling Hosp, Sch Clin Med 1, Dept Neurol, Nanjing 210002, Jiangsu, Peoples R China Univ Sci & Technol China, Affiliated Hosp USTC, Stroke Ctr, Div Life Sci & Med, Hefei 230036, Anhui, Peoples R China Univ Sci & Technol China, Affiliated Hosp USTC, Dept Neurol, Hefei 230036, Anhui, Peoples R China Guilin Peoples Hosp, Dept Neurol, Guilin 541002, Guangxi, Peoples R China Peking Univ, Inst Cardiovasc Sci, Beijing 100191, Peoples R China Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China Peking Univ, Sch Basic Med, Inst Cardiovasc Sci, Hlth Sci Ctr, Beijing 100191, Peoples R China Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Dept Neurol, Shenzhen 518035, Guangdong, Peoples R China |
| Keywords | MICROPARTICLES CELLS EXOSOMES INFLAMMATION CORONARY FLOW RISK |
| Issue Date | Aug-2022 |
| Publisher | CELLULAR AND MOLECULAR LIFE SCIENCES |
| Abstract | Most cells involved in atherosclerosis release extracellular vesicles (EVs), which can carry bioactive substances to downstream tissues via circulation. We hypothesized that EVs derived from atherosclerotic plaques could promote atherogenesis in remote locations, a mechanism that mimics the blood metastasis of cancer. Ldlr gene knockout (Ldlr KO) rats were fed on a high cholesterol diet and underwent partial carotid ligation to induce local atherosclerosis. EVs were separated from carotid artery tissues and downstream blood of carotid ligation by centrifugation. MiRNA sequencing and qPCR were then performed to detect miRNA differences in EVs from rats with and without induced carotid atherosclerosis. Biochemical analyses demonstrated that EVs derived from atherosclerosis could increase the expression of ICAM-1, VCAM-1, and E-selectin in endothelial cells in vitro. EVs derived from atherosclerosis contained a higher level of miR-23a-3p than those derived from controls. MiR-23a-3p could promote endothelial inflammation by targeting Dusp5 and maintaining ERK1/2 phosphorylation in vitro. Inhibiting EV release could attenuate atherogenesis and reduce macrophage infiltration in vivo. Intravenously administrating atherosclerotic plaque-derived EVs could induce intimal inflammation, arterial wall thickening and lumen narrowing in the carotids of Ldlr KO rats, while simultaneous injection of miR-23a-3p antagomir could reverse this reaction. The results suggested that EVs may transfer atherosclerosis to remote locations by carrying proinflammatory factors, particularly miR-23a-3p. |
| URI | http://hdl.handle.net/20.500.11897/649322 |
| ISSN | 1420-682X |
| DOI | 10.1007/s00018-022-04464-2 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 分子心血管学教育部重点实验室 |
