| First Author | Mill C | Year | 2014 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 34 |
| Issue | 11 | Pages | 2449-56 |
| PubMed ID | 25212236 | Mgi Jnum | J:230475 |
| Mgi Id | MGI:5760121 | Doi | 10.1161/ATVBAHA.114.303922 |
| Citation | Mill C, et al. (2014) Wnt5a-induced Wnt1-inducible secreted protein-1 suppresses vascular smooth muscle cell apoptosis induced by oxidative stress. Arterioscler Thromb Vasc Biol 34(11):2449-56 |
| abstractText | OBJECTIVE: Apoptosis of vascular smooth muscle cells (VSMCs) contributes to thinning and rupture of the atherosclerotic plaque fibrous cap and is thereby associated with myocardial infarction. Wnt protein activation of beta-catenin regulates numerous genes that are associated with cell survival. We therefore investigated Wnt/beta-catenin survival signaling in VSMCs and assessed the presence of this pathway in human atherosclerotic plaques at various stages of the disease process. APPROACH AND RESULTS: Wnt5a induced beta-catenin/T-cell factor signaling and retarded oxidative stress (H(2)O(2))-induced apoptosis in mouse aortic VSMCs. Quantification of mRNA levels revealed a >4-fold (P<0.05; n=9) increase in the expression of the Wnt/beta-catenin responsive gene, Wnt1-inducible secreted protein-1 (WISP-1), which was dependent on cAMP response element-binding protein and sustained in the presence of H(2)O(2). Exogenous WISP-1 significantly reduced H(2)O(2)-induced apoptosis by 43% (P<0.05; n=3) and was shown using silencing small interfering RNA, to be important for Wnt5a-dependent survival responses to H(2)O(2) (P<0.05; n=3). WISP-1 protein levels were significantly lower ( approximately 50%) in unstable atherosclerosis compared with stable plaques (n=11 and n=14). CONCLUSIONS: These results indicate for the first time that Wnt5a induces beta-catenin survival signaling in VSMCs via WISP-1. The deficiency of the novel survival factor, WISP-1 in intimal VSMCs of unstable coronary plaques, suggests that there is altered Wnt/beta-catenin/ T-cell factor signaling with progressive atherosclerosis, and restoration of WISP-1 protein might be an effective stabilization factor for vulnerable atherosclerotic plaques. |
