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

Molecular Therapy: Nucleic Acids

Wei Zhang¹  Yuan Qi¹  Hui Huang¹  Zhenxing Xu¹  Hairong Wang¹  Chenjun Zhang¹  Shengqiong Deng²  Mei Jiang³ 

[1] Department of Cardiology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. China;Department of Clinical Laboratory, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. China;Department of Neurology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. China;

关键词: acute myocardial infarction;    Sirtuin 1;    adipose-tissue-derived stem cells;    exosomes;    Nrf2;    chemokine receptor CXCR7;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown