Abstract 250: Potential Plaque Stabilizing Effects of IGF-1 in Atherosclerosis
The role of insulin-like growth factor-1 (IGF-1) in atherosclerosis remains unclear. Whereas some studies report a potential anti-atherogenic effect of this hormone, others point towards an unfavorable role in atherogenesis. Impaired IGF-1 signalling has also been implicated in increased apoptosis of plaque smooth muscle cells, which can be regarded as an important factor in destabilization of advanced plaques by thinning of the protective fibrous cap. Most of the evidence thus far has been circumstantial, however, and we therefore studied the effects of administration of an IGF-1 homologue (long R3 IGF-1), in an atherosclerotic mouse model. ApoE−/ − mice were fed a Western-type diet and perivascular collars were placed around the carotid arteries to accelerate atherogenesis. One week after collar placement, osmotic pumps were implanted subcutaneously to deliver a continuous infusion of long R3 IGF-1 (long R3 IGF-1: n=11; control: n=15). 4 weeks after pump implantation, the mice were sacrificed and collar-induced atherosclerotic plaques were analyzed morphometrically and immunohistochemically. The degree of stenosis was found to be reduced by 33.7% (p=0.018, Mann-Whitney test) following long R3 IGF-1 treatment, whereas the cap/plaque ratio was increased by 40.1% (p=0.008), implying increased plaque stability. Long R3 IGF-1 increased staining for smooth muscle cell actin increased by 48.6% (p=0.085). The observed overall decrease in stenosis may be regarded as important when considering potential long-term benefits of IGF-1 in atherosclerosis. The noted effect on plaque morphology, on the other hand, points towards a potentially more practical short-term use of IGF-1 as a plaque stabilizing treatment.