title: Low circulating insulin-like growth factor I increases atherosclerosis in ApoE-deficient mice.
abstract: Some clinical studies have suggested that lower IGF-I levels may be associated with an increased risk of ischemic heart disease. We generated atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice with 6T alleles (6T/ApoE(-/-) mice) with a 20% decline in circulating IGF-I and fed these mice and control ApoE(-/-) mice with normal chow or a Western diet for 12 wk to evaluate the effect of low serum IGF-I on atherosclerosis progression. We found that the 6T/ApoE(-/-) phenotype was characterized by an increased atherosclerotic burden, elevated plaque macrophages, and increased proinflammatory cytokine TNF-α levels compared with ApoE(-/-) controls. 6T/ApoE(-/-) mice had similar body weight, blood pressure, serum total cholesterol levels, total plaque and smooth muscle cell apoptosis rates, and circulating levels of endothelial progenitor cells as ApoE(-/-) mice. 6T/ApoE(-/-) mice fed with normal chow had reduced vascular endothelial nitric oxide synthase mRNA levels and a trend to increased aortic expression of chemokine (C-C motif) receptor (CCR)1, CCR2, and monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2. Western diet-fed 6T/ApoE(-/-) mice had a trend to increased expression of macrophage scavenger receptor-1/scavenger receptor-A, osteopontin, ATP-binding cassette (subfamily A, member 1), and angiotensin-converting enzyme and elevated circulating levels of the neutrophil chemoattractant chemokine (C-X-C motif) ligand 1 (KC). Our data establish a link between lower circulating IGF-I and increased atherosclerosis that has important clinical implications.
authors.affiliation: Tulane University Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, Louisisana, USA.
authors.forename: Shaw-Yung
authors.initials: SY
authors.lastname: Shai
authors.forename: Sergiy
authors.initials: S
authors.lastname: Sukhanov
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Higashi
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vaughn
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: Patrice
authors.initials: P
authors.lastname: Delafontaine
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D050197:Atherosclerosis / Q000453:epidemiology* / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol