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Differential requirement for nitric oxide in IGF‐1‐induced anti‐apoptotic, anti‐oxidant and anti‐atherosclerotic effects
Author(s) -
Sukhanov Sergiy,
Higashi Yusuke,
Shai Shaw-Yung,
Blackstock Christopher,
Galvez Sarah,
Vaughn Charlotte,
Titterington Jane,
Delafontaine Patrick
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.08.029
Subject(s) - nitric oxide , nitric oxide synthase , endocrinology , medicine , oxidative stress , apoptosis , chemistry , saline , apolipoprotein e , growth factor , lipoprotein lipase , receptor , biochemistry , adipose tissue , disease
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‐α 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.