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Adipose derived mesenchymal stem cell exosomes inhibit adverse ventricular remodeling after myocardial infarction by regulating autophagy and NLRP3 inflammasomes balance of cardiac fibroblasts
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Affiliation:

1.Department of Orthopedics, the First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, China;2.The Second Ward of Cardiology Department, Gansu Provincial Hospital, Lanzhou, Gansu 730000, China;3.Department of Cardiovascular Medicine, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China;4.Department of Emergency, Gansu Provincial Hospital, Lanzhou, Gansu 730000, China;5.Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China)

Clc Number:

R543.3；R363

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    Abstract:

    Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell (ADMSC) exosomes (Exo) on adverse ventricular remodeling after myocardial infarction (MI). Methods The changes of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed. MI rats were injected with an equal volume of normal saline, adipose derived mesenchymal stem cell exosomes (MSC-Exo) or fibroblast exosomes (MEF-Exo) via a tail vein. The expression of autophagy related 16 like protein 1 (ATG16L1), autophagy related protein 7 (ATG7) and NOD-like receptor protein 3 (NLRP3), inflammatory response, the degree of myocardial fibrosis, and the cardiac function were observed in different groups. Results After treatment with H2O2 on cardiac fibroblasts, the expressions of ATG16L1 and ATG7 were significantly decreased (P＜0.001), NLRP3 was significantly increased (P＜0.001), and the levels of inflammatory cytokines interleukin-1β (IL-1β) and IL-18 were significantly elevated (P＜0.001). After MI rats were intervened with MSC-Exo, the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated (P＜0.001), NLRP3 was significantly down-regulated (P＜0.001), serum IL-1β and IL-18 levels were significantly decreased (P＜0.001), fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced (P＜0.001), myocardial fibrosis was significantly relieved (P＜0.001), and cardiac function was significantly improved (P＜0.001). Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.

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WANG Jianjun, LI Jing, MA Xuming, WAN Zhaofei, ZHU Bin, LIU Yaping, GUO Xiangqian, PAN Jiping, FAN Yan. Adipose derived mesenchymal stem cell exosomes inhibit adverse ventricular remodeling after myocardial infarction by regulating autophagy and NLRP3 inflammasomes balance of cardiac fibroblasts[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2024,32(8):654-662.

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  • Received:October 24,2023
  • Revised:February 19,2024
  • Online: August 21,2024
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