title: Increased diet-induced fatty streak formation in female mice with deficiency of liver-derived insulin-like growth factor-I.
abstract: The role of endocrine IGF-I for atherosclerosis is unclear. We determined the importance of circulating, liver-derived IGF-I for fatty streak formation in mice. Mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by approximately 80 %) and control mice received an atherogenic (modified Paigen) diet between 6 and 12 months of age. At study end, Oil Red O staining of aortic root cryosections showed increased fatty streak area and lipid deposition in female but not in male LI-IGF-I(-/-) mice compared to controls. Mac-2 staining of aortic root and measurements of CD68 mRNA level in femoral artery revealed increased macrophage accumulation in proportion to the increased fatty streak area in female LI-IGF-I(-/-) mice. Moreover, female LI-IGF-I(-/-) mice displayed increased serum cholesterol and interleukin-6 as well as increased vascular cell-adhesion molecule 1 (VCAM1) mRNA levels in the femoral artery and elevated VCAM1 protein expression in the aortic root. Thus, increased diet-induced fatty streak formation in female LI-IGF-I(-/-) mice was associated with increased serum cholesterol and signs of systemic inflammation, endothelial activation, lipid deposition, and macrophage infiltration in the vascular wall.
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Göteborg, Sweden. johan.svensson@medic.gu.se.|Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, 413 45, Göteborg, Sweden. johan.svensson@medic.gu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Göteborg, Sweden.
authors.forename: Klara
authors.initials: K
authors.lastname: Sjögren
authors.affiliation: Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Göteborg, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Levin
authors.affiliation: Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Göteborg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.affiliation: Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Göteborg, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Tivesten
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Göteborg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012737:Sex Factors
chemical_list: D015850:Interleukin-6; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol
keywords: Endothelial dysfunction; Fatty streak; IGF-I; Inflammation; Liver derived; Paigen diet