Electroacupuncture pre-treatment exerts a protective effect on LPS-induced cardiomyopathy in mice through the delivery of miR-381 via exosomes

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2024-06, Vol.1870 (5), p.167208, Article 167208
• Main Authors: Chen, Yong, Chen, Shuangli, Zhang, Jingyu, Hu, Xiyou, Li, Ningcen, Liu, Zhen, Huang, Lihong, Yu, Jianbo, Zhang, Yuan, Lin, Xiaowei, Xu, Zhifang, Fang, Yuxin, Chen, Zelin, Guo, Yi, Chen, Bo
• Format: Article
• Language: English
• Subjects: Cardioprotection; Electroacupuncture; LPS-induced cardiomyopathy; Molecular mechanism; Pre-treatment
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167208

This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381. •EA pre-treatment demonstrated an improvement in the survival rate of septic mice.•EA pre-treatment confers a protective impact on sepsis-induced cardiac dysfunction.•Exosomes are vital in mediating the cardioprotective effects induced by EA pre-treatment.•miR-381 is a potential target for treating sepsis-induced cardiac dysfunction.