title: Spontaneous experimental atherosclerosis in hypercholesterolemic mice advances with ageing and correlates with mitochondrial reactive oxygen species.
abstract: Ageing and atherosclerosis are associated with oxidative stress. Mitochondrial redox function declines with ageing. Here we tested whether ageing LDL receptor knockout mice (LDLr-/-) develop spontaneous atherosclerosis and whether mitochondrial reactive oxygen species (mtROS) correlate with atherosclerosis. Compared with young mice, aged LDLr-/-mice exhibited 20-fold larger aortic lesion size, although the plasma cholesterol levels did not vary between age groups. The lesion sizes increased exponentially from 3 to 24months of age (r=0.92, p=0.0001) and were correlated with mtROS across the age range (r=0.81, p=0.0001). Thus, LDLr-/-mice develop spontaneous diet-independent atherosclerosis, that advances exponentially with ageing. We propose that age related increases in mtROS contribute to accelerate atherosclerosis development in hypercholesterolemic mice.
authors.affiliation: Dept of Structural and Functional Biology, Biology Institute, Campinas, SP, Brazil.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Dorighello
authors.affiliation: Dept of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Paim
authors.affiliation: Dept of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Ana Catarina R
authors.initials: ACR
authors.lastname: Leite
authors.affiliation: Dept of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
authors.affiliation: Dept of Structural and Functional Biology, Biology Institute, Campinas, SP, Brazil. Electronic address: ho98@g.unicamp.br.
authors.forename: Helena C F
authors.initials: HCF
authors.lastname: Oliveira
mesh_terms: D000375:Aging; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D006937:Hypercholesterolemia / Q000150:complications*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011973:Receptors, LDL / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D011973:Receptors, LDL
keywords: Atherosclerosis; Hypercholesterolemia; LDL receptor; Mitochondria; Reactive oxygen