The role of insulin growth factor on atherosclerosis and endothelial function: The effect on hyperlipidemia and aging

Aims: Insulin/insulin-like growth factor (IGF-1) signaling is important for a variety of age-related processes. However, whether or not it affects atherosclerosis is unknown. Main methods: Six groups of 6 male New Zealand white rabbits were treated for 12 weeks under the following conditions: Groups YC and YIGF: Young rabbits (10 weeks old) were fed regular chow w/wo IGF-1 (Somazon0.1 mg/kg/day. s.c.). Groups HC and HIGF: young rabbits were fed HCD (0.5% cholesterol plus regular chow) w/wo IGF-1. Groups OC and OIGF: old rabbits (120 weeks old) were fed regular chow w/wo IGF-1. Key findings: Plasma lipid levels, endothelial responses and morphological findings did not differ between groups YIGF and YC. Animals in group HC had increased plasma lipid levels and atheromas. In group HIGF, IGF led to atheromas with increased plasma insulin growth factor binding protein 3 (IBP3), inducible nitric oxide synthase (iNOS) expression and nitrotyrosine staining, macrophage staining, SM1 staining and SM embryo staining compared to HC. Basal nitric oxide (NO) release evaluated by plasma NO metabolites (NOx) and cGMP levels were lowest in the HIGF group. Significance: Overall, IGF-1 promoted atherosclerosis by affecting endothelial function and aging. These findings indicate that Insulin/IGF1 may contribute to atherogenesis in the elderly. (C) 2011 Elsevier Inc. All rights reserved.