title: Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects.
abstract: 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.
authors.affiliation: Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, LA 70112, USA. ssukhano@tulane.edu
authors.forename: Sergiy
authors.initials: S
authors.lastname: Sukhanov
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Higashi
authors.forename: Shaw-Yung
authors.initials: SY
authors.lastname: Shai
authors.forename: Christopher
authors.initials: C
authors.lastname: Blackstock
authors.forename: Sarah
authors.initials: S
authors.lastname: Galvez
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vaughn
authors.forename: Jane
authors.initials: J
authors.lastname: Titterington
authors.forename: Patrick
authors.initials: P
authors.lastname: Delafontaine
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D052250:Nitric Oxide Synthase Type III; D008071:Lipoprotein Lipase; D019331:NG-Nitroarginine Methyl Ester