2. Academic Validation
  3. Blocking exosomal miRNA-153-3p derived from bone marrow mesenchymal stem cells ameliorates hypoxia-induced myocardial and microvascular damage by targeting the ANGPT1-mediated VEGF/PI3k/Akt/eNOS pathway

Blocking exosomal miRNA-153-3p derived from bone marrow mesenchymal stem cells ameliorates hypoxia-induced myocardial and microvascular damage by targeting the ANGPT1-mediated VEGF/PI3k/Akt/eNOS pathway

  • Cell Signal. 2021 Jan;77:109812. doi: 10.1016/j.cellsig.2020.109812.
Wenlong Ning 1,  Shuhua Li 2,  Weiguang Yang 1,  Bo Yang 3,  Chuanyou Xin 1,  Xin Ping 1,  Chuanqi Huang 1,  Yan Gu 1,  Longzhe Guo 4
Affiliations

Affiliations

  • 1 Department of Emergency, the First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang, China; Department of Emergency, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar 161000, Heilongjiang, China.
  • 2 Department of Emergency, the First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang, China; Department of Traditional Chinese Medicine, the First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang, China; Department of Traditional Chinese Medicine, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang, China.
  • 3 Department of Traditional Chinese Medicine, the First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang, China; Department of Traditional Chinese Medicine, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang, China.
  • 4 Department of Emergency, the First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang, China; Department of Emergency, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar 161000, Heilongjiang, China; Department of Anatomy, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, Heilongjiang, China. Electronic address: guolongzhe2@163.com.
PMID: 33164880 DOI: 10.1016/j.cellsig.2020.109812
Abstract

It has been widely reported that exosomes derived from mesenchymal stem cells (MSCs) have a protective effect on myocardial infarction (MI). However, the specific molecules which play a damaging role in MSCs shuttled miRNAs are much less explored. MiRNA-153-3p (miR-153-3p) is a vital miRNA which has been proved to modulate cell proliferation, Apoptosis, angiogenesis, peritoneal fibrosis and aortic calcification. Here, we aim to study the effect and mechanism of miR-153-3p in MSC-derived exosomes on hypoxia-induced myocardial and microvascular damage. The exosomes of MSCs were isolated and identified, and the MSCs-exosomes with low expression of miR-153-3p (exo-miR-153-3p-) were constructed to interfere with the endothelial cells and cardiomyocytes in the oxygen-glucose deprivation (OGD) model. The viability, Apoptosis, angiogenesis of endothelial cells and cardiomyocytes were determined. Additionally, ANGPT1/VEGF/VEGFR2/KDR/Flk-1/PI3K/Akt/eNOS pathway was detected by ELISA and/or western blot. The results illustrated that exo-miR-153-3p- significantly reduced the Apoptosis of endothelial cells and cardiomyocytes and promoted their viability. Meanwhile, exo-miR-153-3p- can promote the angiogenesis of endothelial cells. Mechanistically, miR-153-3p regulates the VEGF/VEGFR2/KDR/Flk-1/PI3K/Akt/eNOS pathways by targeting ANGPT1. Intervention with VEGFR2/KDR/Flk-1 inhibitor (SU1498, 1 μM) remarkably reversed the protective effect of exo-miR-153-3p- in vascular endothelial cells and cardiomyocytes treated by OGD. Collectively, MSCs-derived exosomes with low-expressed miR-153-3p notably promotes the activation of ANGPT1 and the VEGF/VEGFR2/KDR/Flk-1 /PI3K/Akt/eNOS pathways, thereby preventing the damages endothelial cells and cardiomyocytes against hypoxia.

Keywords

ANGPT1; Exosome; Mesenchymal stem cells; Myocardial damage; miR-153-3p.

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