title: Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice.
abstract: Cytomegalovirus (CMV) infection has been associated with coronary artery disease, but it is unknown whether the virus can causally contribute to atherogenesis. To determine whether the virus has this capacity, we infected an atherosclerotic-prone mouse strain (C57BL/6J apoE-/-) with murine CMV. At 14 days of age, 30 mice received CMV (30000 pfu) ip and 30 received virus free media. At 13 and 16 weeks atherosclerotic lesion size was measured from aortic sinus cross-sections. Infection did not alter plasma levels of cholesterol, triglycerides, and high density lipoprotein (HDL); however, 4 weeks after infection IFNgamma levels were elevated (infection vs control: 156+/-49 vs 50+/-22 pg/ml, P=0.04). No differences in lesion size were present at 13 weeks post infection. However, by 16 weeks mean aortic sinus lesion area (mm(2)x10(3)+/-SEM; N=75) in the CMV-infected mice was significantly greater than in uninfected mice (74+/-6 vs 57+/-6; P=0.04). CMV caused the greatest increase (34%) in lesion size in females (103+/-9 vs 77+/-10; P=0.05; N=35). These results provide additional evidence implicating CMV as a causal agent of atherosclerosis, at least in an animal model.
authors.affiliation: Cardiology Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hsich
authors.forename: Y F
authors.initials: YF
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Paigen
authors.forename: T M
authors.initials: TM
authors.lastname: Johnson
authors.forename: M S
authors.initials: MS
authors.lastname: Burnett
authors.forename: S E
authors.initials: SE
authors.lastname: Epstein
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000150:complications*; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D012016:Reference Values; D012850:Sinus of Valsalva / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D007371:Interferon-gamma