Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120301967 |
| _version_ | 1811226096573612032 |
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| author | Hui Huang Zhenxing Xu Yuan Qi Wei Zhang Chenjun Zhang Mei Jiang Shengqiong Deng Hairong Wang |
| author_facet | Hui Huang Zhenxing Xu Yuan Qi Wei Zhang Chenjun Zhang Mei Jiang Shengqiong Deng Hairong Wang |
| author_sort | Hui Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:18:34Z |
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| id | doaj.art-aba9313b91bb46649467f3f338a4b5cd |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-12T09:18:34Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-aba9313b91bb46649467f3f338a4b5cd2022-12-22T03:38:44ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-09-0121737750Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCsHui Huang0Zhenxing Xu1Yuan Qi2Wei Zhang3Chenjun Zhang4Mei Jiang5Shengqiong Deng6Hairong Wang7Department of Cardiology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. ChinaDepartment of Cardiology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. ChinaDepartment of Cardiology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. ChinaDepartment of Cardiology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. ChinaDepartment of Cardiology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. ChinaDepartment of Neurology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. ChinaDepartment of Clinical Laboratory, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. ChinaDepartment of Cardiology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, P.R. China; Corresponding author: Hairong Wang, Department of Cardiology, Shanghai Gongli Hospital, The Second Military Medical University, 219 Miao-Pu Road, Shanghai 200135, P.R. China.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.http://www.sciencedirect.com/science/article/pii/S2162253120301967acute myocardial infarctionSirtuin 1adipose-tissue-derived stem cellsexosomesNrf2chemokine receptor CXCR7 |
| spellingShingle | Hui Huang Zhenxing Xu Yuan Qi Wei Zhang Chenjun Zhang Mei Jiang Shengqiong Deng Hairong Wang Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs Molecular Therapy: Nucleic Acids acute myocardial infarction Sirtuin 1 adipose-tissue-derived stem cells exosomes Nrf2 chemokine receptor CXCR7 |
| title | Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs |
| title_full | Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs |
| title_fullStr | Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs |
| title_full_unstemmed | Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs |
| title_short | Exosomes from SIRT1-Overexpressing ADSCs Restore Cardiac Function by Improving Angiogenic Function of EPCs |
| title_sort | exosomes from sirt1 overexpressing adscs restore cardiac function by improving angiogenic function of epcs |
| topic | acute myocardial infarction Sirtuin 1 adipose-tissue-derived stem cells exosomes Nrf2 chemokine receptor CXCR7 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120301967 |
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