低强度脉冲超声
细胞生物学
胞外囊泡
免疫系统
炎症
医学
癌症研究
化学
免疫学
小RNA
微泡
生物
超声波
生物化学
放射科
基因
治疗性超声
作者
Ping Sun,Yi Li,Yifei Li,Huan Ji,Ge Mang,Shuai Fu,Shuangquan Jiang,Stephen Yiu Chuen Choi,Xiaoqi Wang,Zhonghua Tong,Chao Wang,Fei Gao,Pui‐Ki Wan,Shuang Chen,You Li,Peng Zhao,Xiaoping Leng,Maomao Zhang,Jiawei Tian
出处
期刊:Cardiovascular Research
[Oxford University Press]
日期:2024-05-02
摘要
Abstract Aims CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms. Methods and results In iDCM mice, LIPUS treatment reduced cardiac remodelling and dysfunction. Additionally, CD4+ T cell inflammatory responses were suppressed. LIPUS increased Treg cells while decreasing Th17 cells. LIPUS mechanically stimulates endothelial cells, resulting in increased secretion of extracellular vesicles (EVs), which are taken up by CD4+ T cells and alter their differentiation and metabolic patterns. Moreover, EVs selectively loaded with microRNA (miR)-99a are responsible for the therapeutic effects of LIPUS. The hnRNPA2B1 translocation from the nucleus to the cytoplasm and binding to caveolin-1 and miR-99a confirmed the upstream mechanism of miR-99a transport. This complex is loaded into EVs and taken up by CD4+ T cells, which further suppress mTOR and TRIB2 expression to modulate cellular differentiation. Conclusion Our findings revealed that LIPUS uses an EV-dependent molecular mechanism to protect against iDCM progression. Therefore, LIPUS is a promising new treatment option for iDCM.
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