[Cardiac progenitor cells-derived exosomes alleviate myocardial injury by regulating Treg cell differentiation through the mTOR pathway in mice with myocardial infarction].

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 CD4T cells were isolated from the spleen of the mice and divided into control group, CD4T 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 CD4IL-10T 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 (<0.001) and CK-MB (=0.0002) and increased percentages of Treg and CD4IL-10T cells. Treatment with CPC-Exos effectively reduced the MI area and lowered serum levels of LDH (=0.003) and CK-MB (=0.003) and the percentages of Tregs (=0.001) and CD4IL-10T cells (=0.004) in the MI mouse models. In the isolated CD4T cells, CPCsExos treatment significantly up-regulated the percentages of Treg (=0.01) and CD4IL-10 T cells (=0.004) and increased the expression of mTOR (=0.009) and p-mTOR (=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.