Affiliation:
1. From the Tulane University Heart and Vascular Institute (S.-Y.S., S.S., Y.H., C.V., P.D.) and the School of Medicine (J.K.), Tulane University School of Medicine, New Orleans, La.
Abstract
Objective—
Growth factors may play a permissive role in atherosclerosis initiation and progression, in part via their promotion of vascular smooth muscle cell (VSMC) accumulation in plaques. However, unstable human plaques often have a relative paucity of VSMC, which has been suggested to contribute to plaque rupture and erosion and to clinical events. Insulin-like growth factor-1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that is a mitogen for VSMC, but when infused into
Apoe
−/−
mice it paradoxically reduces atherosclerosis burden.
Methods and Results—
To determine the effect of stimulation of VSMC growth on atherosclerotic plaque development and to understand mechanisms of IGF-1’s atheroprotective effect, we assessed atherosclerotic plaques in mice overexpressing IGF-1 in smooth muscle cells (SMC) under the control of the α-smooth muscle actin promoter, after backcrossing to the
Apoe
−/−
background (SMP8/
Apoe
−/−
). Compared with
Apoe
−/−
mice, these SMP8/
Apoe
−/−
mice developed a comparable plaque burden after 12 weeks on a Western diet, suggesting that the ability of increased circulating IGF-1 to reduce plaque burden was mediated in large part via non-SMC target cells. However, advanced plaques in SMP8/
Apoe
−/−
mice displayed several features of plaque stability, including increased fibrous cap area, α-smooth muscle actin–positive SMC and collagen content, and reduced necrotic cores.
Conclusion—
These findings indicate that stimulation of VSMC IGF-1 signaling does not alter total atherosclerotic plaque burden and may improve atherosclerotic plaque stability.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
66 articles.
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