Institution: | 1. Departmemt of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China;2. Departmemt of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China;3. Departmemt of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China;4. NHC Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China;5. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, PR China |
Abstract: | Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for myocardial infarction (MI). This study aims to explore the mechanism of human umbilical cord MSCs (hucMSCs)-derived EVs loaded with miR-223 on MI. Inflammation, cell biological functions, and fibrosis in vitro were measured. Furthermore, MI rat models were established to verify the role of EVs-miR-223 in vivo. The binding relationship between miR-223 and P53 was confirmed. ChIP assay was utilized to observe the combination of P53 and S100A9. The suppressed fibrosis of cardiomyocytes occurred with cells overexpressing miR-223. MiR-223 contributed to the angiogenesis of HUVECs. P53 was a target gene of miR-223. In vivo, miR-223 relieved myocardial fibrosis and inflammation infiltration, and promoted the angiogenesis in MI rats. HucMSC-derived EVs loaded with miR-223 mitigates MI and promotes myocardial repair through the P53/S100A9 axis, manifesting the underlying therapy values of hucMSC-derived EVs loaded with miR-223 in MI. |