| First Author | Wang F | Year | 2018 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
| Issue | 7 | Pages | 1468-1478 |
| PubMed ID | 29724817 | Mgi Jnum | J:280131 |
| Mgi Id | MGI:6369295 | Doi | 10.1161/ATVBAHA.118.311059 |
| Citation | Wang F, et al. (2018) Myeloid beta-Catenin Deficiency Exacerbates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice. Arterioscler Thromb Vasc Biol 38(7):1468-1478 |
| abstractText | OBJECTIVE: The Wnt/beta-catenin signaling is an ancient and evolutionarily conserved pathway that regulates essential aspects of cell differentiation, proliferation, migration and polarity. Canonical Wnt/beta-catenin signaling has also been implicated in the pathogenesis of atherosclerosis. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis, but the role of macrophage beta-catenin in atherosclerosis remains elusive. This study aims to investigate the impact of beta-catenin expression on macrophage functions and atherosclerosis development. APPROACH AND RESULTS: To investigate the role of macrophage canonical Wnt/beta-catenin signaling in atherogenesis, we generated beta-catenin(Deltamye)LDLR(-/-) mice (low-density lipoprotein receptor-deficient mice with myeloid-specific beta-catenin deficiency). As expected, deletion of beta-catenin decreased macrophage adhesion and migration properties in vitro. However, deficiency of beta-catenin significantly increased atherosclerotic lesion areas in the aortic root of LDLR(-/-) (low-density lipoprotein receptor-deficient) mice without affecting the plasma lipid levels and atherosclerotic plaque composition. Mechanistic studies revealed that beta-catenin can regulate activation of STAT (signal transducer and activator of transcription) pathway in macrophages, and ablation of beta-catenin resulted in STAT3 downregulation and STAT1 activation, leading to elevated macrophage inflammatory responses and increased atherosclerosis. CONCLUSIONS: This study demonstrates a critical role of myeloid beta-catenin expression in atherosclerosis by modulating macrophage inflammatory responses. |
