Exosomes generated from bone marrow mesenchymal stem cells limit the damage caused by myocardial ischemia-reperfusion via controlling the AMPK/PGC-1α signaling pathway

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-05-05 DOI:10.1016/j.bbadis.2025.167890

Yangping Zhuang , Yu Wang , Xiahong Tang , Nan Zheng , Shirong Lin , Jun Ke , Feng Chen

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Abstract

Myocardial ischemia/reperfusion (I/R) injury is one of the problems after coronary artery recanalization in patients with acute myocardial infarction, and the discovery of exosomes presents a broad potential for treating myocardial I/R injury. This work examined the function and regulatory mechanisms of exosomes produced from bone marrow mesenchymal stem cells (BMSCs-Exo) in myocardial I/R injury. Rats with I/R injuries had their myocardium directly injected with BMSCs-Exo. The outcomes demonstrated that cardiac function was enhanced and BMSCs-Exo dramatically decreased myocardial infarct size. Transcriptome sequencing was performed on heart tissues from the model and exosome-treated groups. GO and KEGG enrichment analyses revealed that exosomes might mitigate myocardial I/R damage via the AMPK/PGC-1α signaling pathway, confirmed by both in vitro and in vivo tests. The findings imply that compound C and sh-AMPK reverse the activation of PGC-1α and its downstream proteins and negate the protective effects of exosomes against oxidative stress and mitochondrial function in damaged cardiomyocytes. On the other hand, p-AMPK expression was unaffected by PGC-1α silencing. It was demonstrated that via activating the AMPK/PGC-1α signaling pathway, BMSCs-Exo might reduce oxidative stress and mitochondrial dysfunction in cardiomyocytes, thereby protecting against myocardial I/R damage.

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骨髓间充质干细胞产生的外泌体通过控制AMPK/PGC-1α信号通路限制心肌缺血-再灌注损伤

心肌缺血再灌注（I/R）损伤是急性心肌梗死患者冠状动脉再通后的问题之一，外泌体的发现为心肌I/R损伤的治疗提供了广阔的前景。本研究探讨了骨髓间充质干细胞（BMSCs-Exo）产生的外泌体在心肌I/R损伤中的功能和调控机制。I/R损伤大鼠心肌直接注射BMSCs-Exo。结果显示心功能增强，BMSCs-Exo显著降低心肌梗死面积。对模型组和外泌体处理组的心脏组织进行转录组测序。GO和KEGG富集分析表明，外泌体可能通过AMPK/PGC-1α信号通路减轻心肌I/R损伤，这一结果得到了体外和体内试验的证实。这些发现表明，化合物C和sh-AMPK逆转了PGC-1α及其下游蛋白的激活，并否定了外泌体对氧化应激和线粒体功能的保护作用。另一方面，p-AMPK的表达不受PGC-1α沉默的影响。结果表明，通过激活AMPK/PGC-1α信号通路，BMSCs-Exo可能降低心肌细胞氧化应激和线粒体功能障碍，从而保护心肌I/R损伤。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.