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Mesenchymal Stem Cell-Derived Extracellular Vesicle-Shuttled microRNA-302d-3p Represses Inflammation and Cardiac Remodeling Following Acute Myocardial Infarction

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Abstract

Our research intended to investigate the roles of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in acute myocardial infarction (AMI) via delivery of microRNA (miR)-302d-3p. AMI mouse models were established. EVs isolated from MSCs with miR-302d-3p mimic were injected near the infarct area or co-cultured with hypoxic cardiomyocytes to evaluate their effects. The expression of NF-κB pathway-related genes and inflammatory factors was determined. AMI mice exhibited downregulated miR-302d-3p and elevated MD2 and BCL6 levels. BCL6 was negatively targeted by miR-302d-3p and could bind to MD2 promoter to upregulate MD2 expression. MSCs-EVs, MSCs-EVs carrying miR-302d-3p, or BCL6 or MD2 silencing inactivated the NF-κB pathway and alleviated infarcted area, myocardial fibrosis, inflammation, apoptosis, and cardiac dysfunction in AMI mice. Besides, MSCs-EVs, MSCs-EVs carrying miR-302d-3p, or BCL6 or MD2 silencing diminished viability and inflammation but augmented apoptosis of hypoxic cardiomyocytes. Conclusively, MSCs-EVs carrying miR-302d-3p repressed inflammation and cardiac remodeling after AMI via BCL6/MD2/NF-κB axis.

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Funding

This study was supported by the Guidance Project of Social Development Plan of Science and Technology Bureau of Qiqihar in 2019 (No. SFZD-2019139).

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Authors and Affiliations

  1. Clinical Laboratory, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, People’s Republic of China

    Yuanyuan Liu, Rongchun Guan, Yueping Zhu, Shiming Sun & Yan Qu

  2. The Fifth Ward of Cardiovascular Medicine, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, People’s Republic of China

    Jizhou Yan

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  1. Yuanyuan Liu
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Correspondence to Yan Qu.

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Animal experiments were conducted under the approval of the Animal Ethics Committee of The Third Affiliated Hospital of Qiqihar Medical University and in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health. Extensive efforts were made to ensure minimal suffering of the included animals.

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Communicated by Associate Editor Yihua Bei oversaw the review of this article.

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Liu, Y., Guan, R., Yan, J. et al. Mesenchymal Stem Cell-Derived Extracellular Vesicle-Shuttled microRNA-302d-3p Represses Inflammation and Cardiac Remodeling Following Acute Myocardial Infarction. J. of Cardiovasc. Trans. Res. 15, 754–771 (2022). https://doi.org/10.1007/s12265-021-10200-1

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