Plasma small extracellular vesicles of ischemic cardiomyopathy aggravate ventricular remodeling post-myocardial infarction through miR-223-3p-mediated dysfunction in regulatory T cells
Ischemic cardiomyopathy (ICM), caused by acute myocardial infarction (AMI), is the most common type of chronic heart failure (HF). Treg cells, maintaining peripheral immune tolerance, are dysfunctional in ICM mice. The mechanism of dysfunctional Treg cells in ICM remains unclear. Furthermore, small extracellular vesicles (sEVs) are significant in intracellular communication and tissue homeostasis. This study tends to illustrate whether plasma sEVs of ICM promote the dysfunctional state of Treg cells through miRNA and thus aggravate cardiac remodeling.In ICM patients, the number of Treg cells was increased while Foxp3 mean fluorescence intensity (MFI) was decreased in peripheral blood, indicating a dysfunctional phenotype of Treg cells. miR-223-3p, identified by sequencing using plasma sEVs of ICM patients, was upregulated and negatively correlated with blood Treg cell number. Additionally, the number of cardiac Treg cells of ICM mice was increased while Foxp3 MFI was decreased. Furthermore, plasma sEVs from ICM mice aggravate ventricular remodeling in mice post-AMI. Besides, ICM-sEVs decreased the number of Treg cells while miR-223-3p knockdown increased the number of them and promoted the expression of Foxp3 in vitro.Plasma sEVs of ICM aggravate ventricular remodeling post-AMI through miR-223-3p-mediated Treg cells dysfunction in ICM. Overall design: ICM-sEVs from patients, isolated using ultrafiltration, and the control group were used for miRNA sequencing to find out miRNAs relevant to Treg cells and ischemic injury