Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2020 Aug 11

PMID 32771925

Citations 34

Authors

Hui Huang

Zhenxing Xu

Yuan Qi

Wei Zhang

Chenjun Zhang

Mei Jiang

Shengqiong Deng

Hairong Wang

Affiliations

Soon will be listed here.

Abstract

Acute myocardial infarction (AMI) is one of the leading causes of mortality in cardiovascular diseases. The aim of this study was to investigate whether exosomes from Sirtuin 1 (SIRT1)-overexpressing adipose-derived stem cells (ADSCs) had a protective effect on AMI. The expression of C-X-C chemokine receptor type 7 (CXCR7) was significantly downregulated in peripheral blood endothelial progenitor cells (EPCs) from AMI patients (AMI-EPCs) compared with that in healthy donors, which coincided with impaired tube formation. The exosomes from SIRT1 overexpression in ADSCs (ADSCs-SIRT1-Exos) increased the expression of C-X-C motif chemokine 12 (CXCL12) and nuclear factor E2 related factor 2 (Nrf2) in AMI-EPCs, which promoted migration and tube formation of AMI-EPCs, and overexpression of CXCR7 helped AMI-EPCs to restore the function of cell migration and tube formation. Moreover, CXCR7 was downregulated in the myocardium of AMI mice, and knockout of CXCR7 exacerbated AMI-induced impairment of cardiovascular function. Injection of ADSCs-SIRT1-Exos increased the survival and promoted the recovery of myocardial function with reduced infarct size and post-AMI left ventricular remodeling, induced vasculogenesis, and decreased AMI-induced myocardial inflammation. These findings showed that ADSCs-SIRT1-Exos may recruit EPCs to the repair area and that this recruitment may be mediated by Nrf2/CXCL12/CXCR7 signaling.

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