Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects

作者：Sukhanov Sergiy^*; Higashi Yusuke; Shai Shaw Yung; Blackstock Christopher; Galvez Sarah; Vaughn Charlotte; Titterington Jane; Delafontaine Patrick

来源：FEBS LETTERS, 2011, 585(19): 3065-3072.

DOI：10.1016/j.febslet.2011.08.029

• Atherosclerosis
• Nitric oxide
• Growth factors
• Apoptosis
• Oxidative stress

We have shown previously that insulin like-growth factor I (IGF-1) suppressed atherosclerosis in Apoe (/) mice and activated endothelial nitric oxide (NO) synthase. To determine whether IGF-1-induced atheroprotection depends on NO, IGF-1- or saline-infused mice were treated with L-NAME, the pan-NO synthase inhibitor or with D-NAME (control). IGF-1 reduced atherosclerosis in both the D-NAME and L-NAME groups suggesting that IGF-1's anti-atherogenic effect was NO-independent. IGF-1 increased plaque smooth muscle cells, suppressed cell apoptosis and downregulated lipoprotein lipase and these effects were also NO-independent. On the contrary, IGF-1 decreased oxidative stress and suppressed TNF-alpha levels and these effects were blocked by L-NAME. Thus IGF-1's anti-oxidant effect is dependent on its ability to increase NO but is distinct from its anti-atherosclerotic effect which is NO-independent. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

• 出版日期2011-10-3