Atopic dermatitis (AD) is an intensely pruritic dermatosis that develops most commonly during early infancy and childhood and may follow a chronic, relapsing course into adulthood. As a chronic disease, AD requires treatment over an extended period of time, and is therefore difficult to treat. The main difficulty stems from poor adherence to treatment by patients for reasons such as frustration with medication efficacy, inconvenience, and fear of side effects. Methods that improve adherence include creating therapeutic plans with patient preferences in mind, early follow-up visit, increasing patient education through workshops, and discussing with patients and their caretakers their fears about treatment methods. AD can be exceedingly detrimental to a patient's quality of life. Simple measures to improve adherence may improve patients' treatment outcomes and quality of life.
Objective
Insulin-like growth factor 1 (IGF-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 IGF-1 receptor (IGF-1R) deficiency in SMC and fibroblasts (SM22α-CreKI/IGF1R-flox mice). IGF-1R was decreased in the aorta and adventitia of SM22α-CreKI/IGF1R-flox mice and also in aortic SMC, embryonic, skin and lung fibroblasts (FB) isolated from SM22α-CreKI/IGF1R-flox mice. IGF-1R deficiency downregulated collagen mRNA-binding protein LARP6 and vascular collagen, and mice exhibited growth retardation. The high-fat diet fed SM22α-CreKI/IGF1R-flox mice had increased atherosclerotic burden and inflammatory responses. Alpha smooth muscle actin-positive plaque cells had reduced proliferation and elevated apoptosis. SMC/FB-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 SM22α-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 FB is a critical determinant of normal vascular wall development and atheroprotection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.