Abstract 11537: IGF-1 Reduces Atherosclerosis in Rapacz Pigs

Abstract

Introduction: Cardiovascular disease, including atherosclerosis is the leading cause of mortality in the Western world. We have reported that insulin-like growth factor I (IGF-1) reduced atherosclerosis in the murine model, however it is unknown whether IGF-1 exerts protective effect on human-like atherosclerosis. Hypothesis: Rapacz pigs with familial hypercholesterolemia (FH pigs) fed with high-cholesterol diet develop human-like advanced plaques in coronary arteries. We hypothesize that IGF-1 suppresses atherosclerosis in FH pigs. Methods: Human recombinant IGF-1 ( 50 ug/kg) or saline (control) was injected daily into high-fat diet fed FH swine (n=9/group) for 6 months. Atherosclerotic burden was quantified by intravascular ultrasound (IVUS) at basal level (T0), after 3 months on diet (T3) and at sacrificing (T6). Results: IGF-1-injected pigs had 2.6-fold increase in total plasma IGF-1 (ELISA, p<0.001 vs. control pigs). Pigs in IGF-1 and control groups had a gradual increase in vessel volume in the right coronary artery (RCA), and left anterior descending artery (LAD) with time as quantified by IVUS. However, IGF-1-injected pigs had a larger increase in vessel volume after 3 and 6 months compared to controls suggesting vascular hypertrophy. The atherosclerotic burden was increased in RCA, and LAD in both groups after 3 and 6 months of injections compared to the pre-injection time point. We found a significant reduction in atherosclerotic burden in RCA and LAD in IGF-1 group compared to control at 6 months’ time-point (RCA: IGF-1, 203±13%, vs. control, 244±8; LAD: IGF-1, 200±6%, vs. control, 228±11%). The lumen volume of coronaries was decreased in both groups, however, coronaries in IGF-1-injected pigs had on average 24±3% larger lumen volume compared to control pigs at 6 months’ time-point. Conclusions: We found that IGF-1 increased total volume of pig coronaries suggesting hypertrophy and these data are consistent with growth-stimulating effects of IGF-1. We found reduction in atherosclerotic burden and increase in lumen volume in coronaries in the IGF-1 group after 6 months of injections consistent with an anti-atherosclerotic effect of IGF-1. Our data support the feasibility of using IGF-1 for as an anti-atherogenic therapy.