In the present study, normal heart-derived EVs (cEVs) and kidney-derived EVs (nEVs) were isolated and intramyocardially injected into mice after myocardial infarction (MI). We demonstrated that administration of both cEVs and nEVs significantly improved cardiac function, reduced the scar size, and alleviated inflammatory infiltration into the heart. In addition, cardiomyocyte apoptosis was inhibited, whereas angiogenesis was enhanced in the hearts receiving cEVs or nEVs treatment. Moreover, intramyocardial injection of cEVs displayed much better cardiac protective efficacy than nEVs in murine MI models. RNA-seq and protein-protein interaction (PPI) network analysis revealed the protective mRNA clusters in both cEVs and nEVs. These mRNAs were involved in multiple signaling pathways, which may synergistically orchestrate to prevent the heart from further damage post MI.
Collectively, our results indicated that EVs derived from normal heart tissue may represent a promising strategy for cardiac protection in ischemic heart diseases.
结果:在本研究中,分离出正常的心脏源性EV(cEV)和肾脏源性EV(nEV),并在心肌梗死(MI)后对小鼠进行心肌内注射。我们证明了cEV和nEV的给药显著改善了心脏功能,减少了疤痕的大小,并减轻炎症向心脏的浸润。此外,心肌细胞凋亡被抑制,而接受cEVs或nEVs治疗的心脏血管生成增强。此外,在小鼠MI模型中,心肌内注射cEVs比nEVs显示出更好的心脏保护效果。RNA-seq和蛋白质-蛋白质相互作用(PPI)网络分析揭示了cEV和nEV中的保护性mRNA簇。这些mRNA参与多个信号通路,这可能协同协调,以防止心脏在MI后进一步损害。
结论:总的来说,我们的结果表明,来自正常心脏组织的EV可能是缺血性心脏病患者心脏保护的一种有前景的策略.