Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 8.
doi: 10.1007/s12265-025-10623-0. Online ahead of print.

Plasma Small Extracellular Vesicles of Ischemic Cardiomyopathy Aggravate Ventricular Remodeling Post-Myocardial Infarction and Promote miR-223-3p-mediated Dysfunction in Regulatory T Cells

Bifang Mai #  1   2 , Wenlong Jiang #  3 , Jing Yang #  1   2   4 , Yuyang Chen #  1   2 , Zhen Qin  5 , Yuan Li  1   2 , Wenqing Tu  1 , Yuhan Lin  1 , Wai Seng Chan  1 , Jianhua Wu  1 , Fangzhou Cheng  6 , Tao Xu  7 , Shuanglun Xie  8   9
Affiliations

Plasma Small Extracellular Vesicles of Ischemic Cardiomyopathy Aggravate Ventricular Remodeling Post-Myocardial Infarction and Promote miR-223-3p-mediated Dysfunction in Regulatory T Cells

Bifang Mai et al. J Cardiovasc Transl Res. .

Abstract

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.

Keywords: Extracellular vesicles; Ischemic cardiomyopathy; Myocardial infarction; Regulatory T cells; miR-223-3p.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical Approval: All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Sun Yat-Sen University (SYSU-IACUC- 2022–000595). Patient Consent Statement: Informed consent was obtained from all patients included in the study. The study protocol was approved by Medical Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY- 2023–579 - 01), All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Declaration of Generative AI and AI-Assisted Technologies in the Writing Process: The authors did not use generative AI or AI-assisted technologies in the development of this manuscript. Conflict of interest: All authors declare no competing interests.

References

    1. Chang X, Toan S, Li R, Zhou H. Therapeutic strategies in ischemic cardiomyopathy: Focus on mitochondrial quality surveillance. EBioMedicine. 2022;84:104260. https://doi.org/10.1016/j.ebiom.2022.104260 . - DOI - PubMed - PMC
    1. Bagai A, Dangas GD, Stone GW, Granger CB. Reperfusion strategies in acute coronary syndromes. Circ Res. 2014;114:1918–28. https://doi.org/10.1161/CIRCRESAHA.114.302744 . - DOI - PubMed
    1. Stone GW, Selker HP, Thiele H, Patel MR, Udelson JE, Ohman EM, Maehara A, Eitel I, Granger CB, Jenkins PL, Nichols M, Ben-Yehuda O. Relationship between infarct size and outcomes following primary PCI: Patient-level analysis from 10 randomized trials. J Am Coll Cardiol. 2016;67:1674–83. https://doi.org/10.1016/j.jacc.2016.01.069 . - DOI - PubMed
    1. Viola M, de Jager SCA, Sluijter JPG. Targeting inflammation after myocardial infarction: A therapeutic opportunity for extracellular vesicles?. Int J Mol Sci. 2021;22. https://doi.org/10.3390/ijms22157831
    1. Dick SA, Epelman S. Chronic heart failure and inflammation: What do we really know? Circ Res. 2016;119:159–76. https://doi.org/10.1161/CIRCRESAHA.116.308030 . - DOI - PubMed

LinkOut - more resources