on October 4, 2007
Published online before print October 4, 2007, doi: 10.1161/ATVBAHA.107.156257
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Submitted on May 25, 2007
Accepted on September 24, 2007
IGF-1 Reduces Inflammatory Responses, Suppresses, Oxidative Stress and Decreases Atherosclerosis Progression in Apoe-Deficient Mice
Sergiy Sukhanov ;
From the Cardiology Section (S.S., Y.H., S.-Y.S., C.V., J.T., P.D.), Department of Medicine, Tulane University School of Medicine, New Orleans La; the School of Life Sciences (J.M.), Arizona State University, Tempe; the Laboratory of Heart Failure and Stem Cells (Y.L.), Texas Heart Institute, Houston; and the Department of Molecular Pathology (Y.-H.S.), University of Texas M.D. Anderson Cancer Center, Houston.
* To whom correspondence should be addressed. E-mail: pdelafon{at}tulane.edu.
Objective—Whereas growth factors, via their ability to stimulate vascular smooth muscle cell (VSMC) proliferation and migration, have been thought to play a permissive role in atherosclerosis initiation and progression, the role of insulin-like growth factor-1 (IGF-1) is unknown. Here we report for the first time that IGF-1 infusion decreased atherosclerotic plaque progression in ApoE-deficient mice on a Western diet.
Methods and Results—ApoE-null mice (8 weeks) were infused with vehicle or recombinant human IGF-1 and fed a high-fat diet for 12 weeks. Analysis of aortic sinuses revealed that IGF-1 infusion decreased atherosclerotic plaque progression and macrophage infiltration into lesions. Furthermore, IGF-1 decreased vascular expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-
, reduced aortic superoxide formation and urinary 8-isoprostane levels, and increased aortic pAkt and eNOS expression and circulating endothelial progenitor cells, consistent with an antiinflammatory, antioxidant, and prorepair effect on the vasculature.
Conclusions—Our data indicate that an increase in circulating IGF-1 reduces vascular inflammatory responses, systemic and vascular oxidant stress and decreases atherosclerotic plaque progression. These findings have major implications for the treatment of atherosclerosis.
Key words: insulin-like growth factor • atherosclerosis • apolipoprotein E • inflammatory response • oxidative stress
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