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| Molecular Mechanism of SHH/GLI1 Signaling Pathway Regulating Macrophage Pyroptosis in Acute Myocardial Infarction |
| LIAN Ming, GONG Fangna, ZHAO Wanglei |
| The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Hohhot 010059, China |
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Abstract Objective: To explore the possible molecular mechanism of sonic hedgehog (SHH) / glioma-associated oncogene 1 (GLI1) signaling pathway regulating macrophage pyroptosis in acute myocardial infarction (AMI). Methods: Fifty rats were randomly divided into sham operation group, AMI group, SHH inhibition group, macrophage clearance group, macrophage clearance + SHH inhibition group, with 10 rats in each group. Myocardial tissue and serum were collected. Cultured macrophages Raw264.7 were divided into control group, hypoxia group and SHH inhibition group. Masson staining was used to detect myocardial fibrosis level and infarct size. The protein levels of SHH, GLI1, NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), gasdermin-D (GSDMD) were detected by Western blotting. The mRNA levels of SHH, GLI1 and F4/80 were detected by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Serum creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) were detected by enzyme-linked immunosorbent assay (ELISA). Results: Compared with sham operation group, myocardial fibrosis level, infarct size, SHH and GLI1 protein expression, serum CK-MB and LDH contents were significantly increased in AMI group (P<0.05). The expressions of NLRP3, Caspase-1 and GSDMD proteins in myocardial tissue were significantly increased (P<0.05), and the F8/40 mRNA levels in myocardial tissue of macrophage clearance group were significantly decreased (P<0.05), indicating successful macrophage clearance. Compared with AMI group, the myocardial fibrosis level, infarct size and protein expressions of SHH, GLI1, NLRP3, Caspase-1 and GSDMD were significantly decreased in the inhibited SHH group (P<0.05), and the serum CK-MB and LDH contents in the macrophage clearance group were significantly decreased (P<0.05). The serum CK-MB and LDH contents of rats in the macrophage clearance + SHH inhibition group were compared to those in the macrophage clearance group (P<0.05). Compared with the control group, the mRNA levels of SHH and GLI1and the protein expressions of NLRP3, Caspase-1 and GSDMD in macrophages of hypoxia group were significantly increased (P<0.05). Compared with hypoxia group, the mRNA levels of SHH and GLI1 and the protein expressions of NLRP3, Caspase-1 and GSDMD in inhibited SHH group were significantly decreased (P<0.05). Conclusion: Down-regulation of SHH/GLI1 signaling pathway can inhibit macrophage pyroptosis and improve AMI.
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[1] Zhao X,Cao Y,Wu J.Acute inferior myocardial infarction combined with papillary muscle rupture:a case report[J].Zhong Nan Da Xue Xue Bao Yi Xue Ban,2023,48(4):628-632.
[2] Solomonchuk A,Rasputina L,Didenko D.Prevalence,clinical and functional characeristics of patients with acute myocardial infarction comlicated by acute heart failure[J].Wiad Lek,2022,75(7):1741-1746.
[3] Jia D,Chen S,Bai P,et al.Cardiac resident macrophage-derived legumain improves cardiac repair by promoting clearance and degradation of apoptotic cardiomyocytes after myocardial infarction[J].Circulation,2022,145(20):1542-1556.
[4] 贺承莉.复心抑纤汤通过Shh信号通路对心肌梗死后心肌纤维化的影响[D].贵州医科大学,2023.
[5] Zhang J,He Z,Xiong C,et al.SHH induces macrophage oxidative phosphorylation and efferocytosis to promote scar formation[J].Cell Commun Signal,2024,22(1):336.
[6] Nyiramana MM,Cho SB,Kim EJ,et al.Sea hare hydrolysate-induced reduction of human non-small cell lung cancer cell growth through regulation of macrophage polarization and non-apoptotic regulated cell death pathways[J].Cancers (Basel),2020,12(3):726.
[7] Algoet M,Janssens S,Himmelreich U,et al.Myocardial ischemia-reperfusion injury and the influence of inflammation[J].Trends Cardiovasc Med,2023,33(6):357-366.
[8] Ning Y,Huang P,Chen G,et al.Atorvastatin-pretreated mesenchymal stem cell-derived extracellular vesicles promote cardiac repair after myocardial infarction via shifting macrophage polarization by targeting microRNA-139-3p/Stat1 pathway[J].BMC Med,2023,21(1):96.
[9] Cui T,Feng C,Jiang H,et al.Inhibition of PFKFB3 expression stimulates macrophage-mediated lymphangiogenesis post-acute myocardial infarction[J].Front Biosci (Landmark Ed),2023,28(11):277.
[10] Peng H,Chen L,Deng Y,et al.Ginsenoside Rh2 mitigates myocardial damage in acute myocardial infarction by regulating pyroptosis of cardiomyocytes[J].Clin Exp Hypertens,2023,45(1):2229536.
[11] Ma M,Liang SC,Diao KY,et al.Mitofilin mitigates myocardial damage in acute myocardial infarction by regulating pyroptosis of cardiomyocytes[J].Front Cardiovasc Med,2022(9):823591.
[12] Hsu CG,Chavez CL,Zhang C,et al.The lipid peroxidation product 4-hydroxynonenal inhibits NLRP3 inflammasome activation and macrophage pyroptosis[J].Cell Death Differ,2022,29(9):1790-1803. |
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2024, Vol. 30 
