BMSCderived exosomemediated miR253p delivery protects against myocardial ischemia/reperfusion injury by constraining M1like macrophage polarization.
Mol Med Rep
; 30(2)2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38904206
ABSTRACT
Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophagemediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSCExo) harboring miR253p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An in vivo MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSCExo carrying miR253p (BMSCExo253p) were administered through tail vein injection. A hypoxiareoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSCExo253p in vitro. The results of the present study demonstrated that BMSCExo or BMSCExo253p could be taken up by cardiomyocytes in vivo and H9C2 cells in vitro. BMSCExo253p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RTqPCR, such as interleukin1ß (IL1ß) and interleukin6 (IL6). As hypothesized, BMSCExo253p inhibited M1like macrophage polarization and proinflammatory cytokine expression while promoting M2like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R in vivo and in LPSstimulated macrophages in vitro, and BMSCExo253p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSCExo253p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1like macrophage polarization.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myocardial Reperfusion Injury
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MicroRNAs
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STAT3 Transcription Factor
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Exosomes
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Mesenchymal Stem Cells
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Macrophages
Limits:
Animals
Language:
En
Journal:
Mol Med Rep
Year:
2024
Document type:
Article