title: Early atherogenesis in senescence-accelerated mice.
abstract: We studied atheromatous lesion formation in an animal model of accelerated ageing. The senescence-accelerated prone mouse (SAM-P) has a reduced life-span and exhibits clinical features characteristic of human ageing. Our aim was to establish whether these mice are more susceptible to atherosclerosis than a related strain, senescence-accelerated resistant mice (SAM-R), which age normally. We fed a Western-type diet to 14 SAM-P/8 and 14 SAM-R/1 mice for 17 weeks, starting at 28 weeks of age, measuring their serum lipid profiles before and after this diet. We stained aortic root cryostat cross-sections with Oil red O, and assessed lipid deposition morphometrically. We used immunohistochemistry to detect macrophages in the aortic roots. We found that despite showing similar alterations in lipid profile, SAM-P/8 mice developed more prevalent and extensive fatty lesions than SAM-R/1 mice. Furthermore, the lipid lesions in SAM-P/8 mice showed a greater frequency of invasion by macrophages. We conclude that mice, which age at an accelerated rate, are more prone to early atherogenesis than mice which age normally. We suggest that this increased susceptibility may result from abnormalities in the oxidative status and cellular replicative capacity of these mice.
authors.affiliation: The Cell Biology Group at the Centre for Cardiovascular Biology and Medicine, Department of Medicine, University College London, Rayne Building, 5 University Street, London WC1E 6JJ, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Fenton
authors.forename: Hsiu-Lin
authors.initials: HL
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hong
authors.forename: Emma
authors.initials: E
authors.lastname: Hawe
authors.forename: David J
authors.initials: DJ
authors.lastname: Kurz
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Erusalimsky
mesh_terms: D000375:Aging; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D004198:Disease Susceptibility; D005260:Female; D008055:Lipids / Q000032:analysis / Q000097:blood; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal
chemical_list: D008055:Lipids