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Bone Marrow Mesenchymal Stem Cell-Derived Exosomal microRNA-29b-3p Promotes Angiogenesis and Ventricular Remodeling in Rats with Myocardial Infarction by Targeting ADAMTS16

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Abstract

An increasing amount of evidence has suggested that microRNA (miR) plays a role in myocardial infarction (MI). Our study aimed to discuss the impact of exosomal miR-29b-3p in MI by regulating A Disintegrin and Metalloproteinase with Thrombospondin Motifs 16 (ADAMTS16). Exosomes were extracted from bone marrow mesenchymal stem cells (BMSCs). In a rat model of MI, myocardial angiogenesis and ventricular remodeling-related factors, as well as myocardial fibrosis, collagen volume fraction (CVF), capillary density, level of vascular endothelial growth factor (VEGF), and apoptosis of cardiomyocytes, were tested. ADAMTS16 and miR-29b-3p levels in the myocardial tissue of MI rats were tested. miR-29b-3p expression was decreased and ADAMTS16 expression was increased in the myocardial tissue of MI rats. ADAMTS16 was a target gene of miR-29b-3p. Upregulated miR-29b-3p delivered by BMSC-derived exosomes improved myocardial angiogenesis and ventricular remodeling, reduced myocardial fibrosis and CVF, increased capillary density and VEGF expression, and suppressed apoptosis of cardiomyocytes in MI rats. ADAMTS16 overexpression accelerated MI in rats, and ADAMTS16 upregulation reversed the protective effects of miR-29b-3p upregulation on MI rats. Our study provides evidence that upregulated miR-29b-3p delivered by BMSC-secreted exosomes can improve myocardial angiogenesis and ventricular remodeling in rats with MI by targeting ADAMTS16.

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Funding

This work is supported by the Association Foundation Program of Yunnan Provincial Science and Technology Department and Kunming Medical University, Number of scientific research project: 2018FE001 (-285).

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Authors and Affiliations

  1. Department of Cardiology, Fuwai Yunnan Cardiovascular Hospital (The Affiliated Cardiovascular Hospital of Kunming Medical University), Kunming, 650000, Yunnan, China

    Jialin Zheng, Xinjin Zhang, Wenfeng Cai, Yawei Yang, Tao Guo & Jianmei Li

  2. Department of Cardiology, The Second People’s Hospital of Yunnan Province, 176 Qingnan Road, Wuhua District, Kunming, 650000, Yunnan, China

    Hualei Dai

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  1. Jialin Zheng
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Zheng, J., Zhang, X., Cai, W. et al. Bone Marrow Mesenchymal Stem Cell-Derived Exosomal microRNA-29b-3p Promotes Angiogenesis and Ventricular Remodeling in Rats with Myocardial Infarction by Targeting ADAMTS16. Cardiovasc Toxicol 22, 689–700 (2022). https://doi.org/10.1007/s12012-022-09745-7

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