| First Author | Sukhanov S | Year | 2018 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
| Issue | 10 | Pages | 2306-2317 |
| PubMed ID | 30354209 | Mgi Jnum | J:285071 |
| Mgi Id | MGI:6385400 | Doi | 10.1161/ATVBAHA.118.311134 |
| Citation | Sukhanov S, et al. (2018) SM22alpha (Smooth Muscle Protein 22-alpha) Promoter-Driven IGF1R (Insulin-Like Growth Factor 1 Receptor) Deficiency Promotes Atherosclerosis. Arterioscler Thromb Vasc Biol 38(10):2306-2317 |
| abstractText | Objective- IGF-1 (insulin-like growth factor 1) is a major autocrine/paracrine growth factor, which promotes cell proliferation, migration, and survival. We have shown previously that IGF-1 reduced atherosclerosis and promoted features of stable atherosclerotic plaque in Apoe(-/)(-) mice-an animal model of atherosclerosis. The aim of this study was to assess effects of smooth muscle cell (SMC) IGF-1 signaling on the atherosclerotic plaque. Approach and Results- We generated Apoe(-/-) mice with IGF1R (IGF-1 receptor) deficiency in SMC and fibroblasts (SM22alpha [smooth muscle protein 22 alpha]-CreKI/IGF1R-flox mice). IGF1R was decreased in the aorta and adventitia of SM22alpha-CreKI/IGF1R-flox mice and also in aortic SMC, embryonic, skin, and lung fibroblasts isolated from SM22alpha-CreKI/IGF1R-flox mice. IGF1R deficiency downregulated collagen mRNA-binding protein LARP6 (La ribonucleoprotein domain family, member 6) and vascular collagen, and mice exhibited growth retardation. The high-fat diet-fed SM22alpha-CreKI/IGF1R-flox mice had increased atherosclerotic burden and inflammatory responses. alpha-SMA (alpha-smooth muscle actin)-positive plaque cells had reduced proliferation and elevated apoptosis. SMC/fibroblast-targeted decline in IGF-1 signaling decreased atherosclerotic plaque SMC, markedly depleted collagen, reduced plaque fibrous cap, and increased plaque necrotic cores. Aortic SMC isolated from SM22alpha-CreKI/IGF1R-flox mice had decreased cell proliferation, migration, increased sensitivity to apoptosis, and these effects were associated with disruption of IGF-1-induced Akt signaling. Conclusions- IGF-1 signaling in SMC and in fibroblast is a critical determinant of normal vascular wall development and atheroprotection. |
