Abstract: Objective To investigate the effect of cardiac progenitor cells-derived exosomes (CPCs-Exo) on Treg differentiation in mice with myocardial infarction (MI). Methods Mouse models of MI established by ligation of the left anterior descending coronary artery (LAD) were treated with CPCs-Exos, and naive CD4+ T cells were isolated from the spleen of the mice and divided into control group, CD4+T cell activation group (CD3+CD28), CPCs-Exos stimulation group (CD3+CD28+CPCs-Exos), mTOR activator group (CD3+CD28+CPCs-Exos+mTOR activator) and mTOR inhibitor group (CD3+CD28+CPCs-Exos+mTOR inhibitor). Western blotting was used to detect the expression levels of mTOR and p-mTOR in the treated cells. Flow cytometry was used to analyze the percentages of Treg and CD4+ IL-10+ T cells. The infarct size of the mice were measured with 2,3,5-triphenyltetrazole chloride (TTC) staining, and serum levels of LDH and CK-MB were detected using an automatic biochemical analyzer. Results Compared with the control group, the mouse models of MI showed significantly increased release of LDH (P<0.001) and CK-MB (P=0.0002) and increased percentages of Treg and CD4+ IL-10+ T cells. Treatment with CPC-Exos effectively reduced the MI area and lowered serum levels of LDH (P=0.003) and CK-MB (P=0.003) and the percentages of Tregs (P=0.001) and CD4+ IL-10+ T cells (P=0.004) in the MI mouse models. In the isolated CD4+ T cells, CPCs-Exos treatment significantly up-regulated the percentages of Treg (P=0.01) and CD4+IL-10+ T cells (P=0.004) and increased the expression of mTOR (P=0.009) and p-mTOR (P=0.009), and these effects could be further enhanced by the mTOR activator but obviously attenuated by the mTOR inhibitor. Conclusion CPCs-Exos promotes the differentiation of Treg in mice with MI by modulating the mTOR signaling pathway.

Key words: cardiac progenitor cell-derived exosomes; mTOR; Treg; myocardial injury