title: The role of insulin growth factor on atherosclerosis and endothelial function: the effect on hyperlipidemia and aging.
abstract: OBJECTIVE
  Insulin/insulin-like growth factor (IGF-1) signaling is important for a variety of age-related processes. However, whether or not it affects atherosclerosis is unknown.
  
  
  METHODS
  Six groups of 6 male New Zealand white rabbits were treated for 12 weeks under the following conditions: Groups YC and YIGF: Young rabbits (10 weeks old) were fed regular chow w/wo IGF-1(Somazon 0.1 mg/kg/day, s.c.). Groups HC and HIGF: young rabbits were fed HCD (0.5% cholesterol plus regular chow) w/wo IGF-1. Groups OC and OIGF: old rabbits (120 weeks old) were fed regular chow w/wo IGF-1.
  
  
  RESULTS
  Plasma lipid levels, endothelial responses and morphological findings did not differ between groups YIGF and YC. Animals in group HC had increased plasma lipid levels and atheromas. In group HIGF, IGF led to atheromas with increased plasma insulin growth factor binding protein 3 (IBP3), inducible nitric oxide synthase(iNOS) expression and nitrotyrosine staining, macrophage staining, SM1 staining and SM embryo staining compared to HC. Basal nitric oxide (NO) release evaluated by plasma NO metabolites (NOx) and cGMP levels were lowest in the HIGF group.
  
  
  CONCLUSIONS
  Overall, IGF-1 promoted atherosclerosis by affecting endothelial function and aging. These findings indicate that Insulin/IGF1 may contribute to atherogenesis in the elderly.
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. hmatsui@med.nagoya-u.ac.jp
authors.forename: Hisako
authors.initials: H
authors.lastname: Hirai
authors.forename: Rie
authors.initials: R
authors.lastname: Kanaya
authors.forename: Morihiko
authors.initials: M
authors.lastname: Maeda
authors.forename: Ding
authors.initials: D
authors.lastname: Qungfang
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ina
authors.forename: Toshio
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006152:Cyclic GMP / Q000097:blood; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006949:Hyperlipidemias / Q000378:metabolism* / Q000473:pathology; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002791:Cholesterol, Dietary; D018972:Insulin-Like Growth Factor Binding Protein 3; D008055:Lipids; D014665:Vasodilator Agents; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000109:Acetylcholine