Research Paper Volume 12, Issue 4 pp 3682—3693

Exosomes isolated from the plasma of remote ischemic conditioning rats improved cardiac function and angiogenesis after myocardial infarction through targeting Hsp70

Qin Chen 1, 2, 3, *, , Minghan Huang 4, *, , Jiayi Wu 1, 2, 3, , Qiong Jiang 1, 2, 3, , Xingchun Zheng 1, 2, 3, ,

  • 1 Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
  • 2 Fujian Institute of Coronary Artery Disease, Fuzhou, Fujian 350001, P.R. China
  • 3 Fujian Heart Medical Center, Fuzhou, Fujian 350001, P.R. China
  • 4 The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fuzhou, Fujian 350003, P.R. China
* Equal contribution

received: December 27, 2019 ; accepted: January 27, 2020 ; published: February 18, 2020 ;

https://doi.org/10.18632/aging.102837
How to Cite

Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Remote ischemic conditioning (RIC) is a promising therapeutic strategy to protect heart against ischemic-reperfusion injury. Exosomes have been proved to be an important regulator in many pathological processes. Whether the exosomes derived from RIC could improve cardiac remodeling and function after myocardial infarction (MI) has not been reported. MI animal model was established by ligating the left coronary artery. The bilateral hindlimbs of rats were subjected to RIC treatment using tourniquets. Exosomes were isolated from the plasma of RIC rats and identified by transmission electron microscope. The proliferation, migration, and apoptosis of endothelial cells were measured by CCK8, traswell, and flow cytometry. Western blotting, and qRT-PCR were applied to measure the expression of angiogenesis-related molecules, and immunohistochemistry staining was used to observe the expression of vWF. RIC and RIC exosomes remarkably facilitated cardiac function, cardiac cell remodeling, and angiogenesis. RIC exosomes markedly increased the cell ratio in the G1 phase, cell migration, cell proliferation, tube formation, and inhibited cell apoptosis through Hsp70. The expression of eNOS, iNOS, HIF-1α, Ang-1, and VEGF was markedly increased by RIC exosomes. RIC exosomes significantly improved cardiac function, cardiac remodeling, and angiogenesis after MI, and they accelerated angiogenesis through increasing the levels of angiogenesis-related molecules.

Abbreviations

MI: Myocardial infarction; Pre-RIC: RIC before MI; Post-RIC: RIC after the onset of reperfusion; Hsp70: 70-kDa Hsp; eNOS: endothelial nitric oxide synthase; NO: nitric oxide; IL-5: interleukin-5; VEGF: vascular endothelial growth factor; Ang-1: angiopoietin-1; HIF-1 α: hypoxia-inducible factor 1 α; CMVECs: cardiac microvascular endothelial cells; HE: hematoxylin eosin; TEM: Transmission electron microscope; SD: Standard deviation; IL-10: interleukin-10; si-Hsp70: siRNA of Hsp70; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening.