Plasma Small Extracellular Vesicles of Ischemic Cardiomyopathy Aggravate Ventricular Remodeling Post-Myocardial
Bifang Mai1,2, Wenlong Jiang3, Jing Yang1,2,4
1Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China.
Treg dysfunction in ischemic cardiomyopathy (ICM) remains mechanistically unclear. We investigated ICM plasma small extracellular vesicles (ICM-sEVs) in Treg regulation and post-MI remodeling. Flow cytometry assessed Treg frequency. ICM-sEV miRNA sequencing revealed miR-223-3p enrichment, validated using miR-223-/- and Foxp3GFP/+ mice. ICM patients and mice exhibited elevated Treg numbers but suppressed Foxp3. miR-223-3p was upregulated in ICM-sEVs and inversely correlated with functional Tregs. ICM-sEVs administration aggravated ventricular remodeling post myocardial infarction (MI) in mice while reducing Treg frequency and elevating miR-223-3p in vitro. miR-223 knockdown increased Treg cell number and Foxp3 expression, whereas miR-223 overexpression reversed the phenotype. ICM-sEVs aggravate ventricular remodeling post-MI and promote miR-223-3p-mediated Treg cell dysfunction.
Treg dysfunction in ischemic cardiomyopathy (ICM) remains mechanistically unclear. We investigated ICM plasma small extracellular vesicles (ICM-sEVs) in Treg regulation and post-MI remodeling. Flow cytometry assessed Treg frequency. ICM-sEV miRNA sequencing revealed miR-223-3p enrichment, validated using miR-223-/- and Foxp3GFP/+ mice. ICM patients and mice exhibited elevated Treg numbers but suppressed Foxp3. miR-223-3p was upregulated in ICM-sEVs and inversely correlated with functional Tregs. ICM-sEVs administration aggravated ventricular remodeling post myocardial infarction (MI) in mice while reducing Treg frequency and elevating miR-223-3p in vitro. miR-223 knockdown increased Treg cell number and Foxp3 expression, whereas miR-223 overexpression reversed the phenotype. ICM-sEVs aggravate ventricular remodeling post-MI and promote miR-223-3p-mediated Treg cell dysfunction.
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