| First Author | Jia D | Year | 2024 |
| Journal | Exp Cell Res | Volume | 442 |
| Issue | 2 | Pages | 114253 |
| PubMed ID | 39271099 | Mgi Jnum | J:368994 |
| Mgi Id | MGI:7733028 | Doi | 10.1016/j.yexcr.2024.114253 |
| Citation | Jia D, et al. (2024) SIRT1 mediates the inflammatory response of macrophages and regulates the TIMP3/ADAM17 pathway in atherosclerosis. Exp Cell Res 442(2):114253 |
| abstractText | OBJECTIVE: Macrophage polarization and the resulting phenotype have versatile roles in atherosclerosis. The study aims to decipher the role of SIRT1 in regulating macrophage phenotypes and atherosclerosis development. METHODS: Two mouse lines of SIRT1( big up tri, openMac)/ApoE(-/-) and SIRT1(fl/fl)/ApoE(-/-) were fed with high-fat diet to generate atherosclerotic lesion. Mouse peritoneal macrophages were isolated and transfected with SIRT1-overexpressing vector or vector-null. RESULTS: The SIRT1( big up tri, openMac)/ApoE(-/-) mice exhibited greater atherosclerotic lesions, stronger immunofluorescence staining for M1-like macrophage marker, iNOS, and weaker immunofluorescence staining for M2-like macrophage marker, Arginase-1, than the SIRT1(fl/fl)/ApoE(-/-) littermates. The gene expressions of M1 markers (IL-1beta, IL-6, and iNOS) were increased and those of M2 markers (IL-10 and Arg-1) decreased in both aortic roots and peritoneal macrophages from SIRT1( big up tri, openMac)/ApoE(-/-) mice, whereas SIRT1 overexpression rectified the changes in M1/M2 expression. A declined expression of TIMP3 with an increased expression of ADAM17 was noted in SIRT1( big up tri, openMac)/ApoE(-/-) macrophages, whereas SIRT1 overexpression rescued TIMP3 expression and inhibited ADAM17 expression. CONCLUSION: Our data suggest that SIRT1 deficiency may promote macrophage M1 polarization and regulate the TIMP3/ADAM17 pathway thus favoring atherosclerosis development, indicating an anti-atherosclerotic role of macrophage SIRT1. |
