title: Murine cytomegalovirus infection increases aortic expression of proatherosclerotic genes.
abstract: BACKGROUND
  The possible etiologic role of infection in cardiovascular disease is still debated. Having previously demonstrated that murine cytomegalovirus (MCMV) infection of apolipoprotein (apo) E-/- mice increases atherosclerotic lesion size, we determined if MCMV infection produces proatherogenic changes in aortic gene expression. Additionally, in cholesterol-fed C57BL/6J mice, we examined the effects of MCMV infection on aortic lesion area.
  
  
  RESULTS
  C57BL/6J apoE-/- and wild-type C57BL/6J mice were infected with MCMV. At various time points, aortas were collected and pooled. Total RNA was extracted and hybridized to Affymetrix murine chips or analyzed for specific gene expression using TaqMan reverse transcription-polymerase chain reaction. Data from infected and uninfected mice were compared. A separate group of cholesterol-fed C57BL/6J mice were infected with MCMV, and lesion area in the aortic sinus was assessed using oil red O staining. Acute MCMV infection altered aortic expression of atherogenic genes in young apoE-/- and C57BL/6J mice-specifically, monocyte chemoattractant protein-1, monokine induced by interferon-gamma, and interferon-gamma inducible protein 10. Acute infection in adult 9-month-old apoE-/- mice with well-established lesions increased aortic expression of monocyte chemoattractant protein-1. Atherosclerotic lesion area in cholesterol-fed C57BL/6J mice was increased after infection with MCMV.
  
  
  CONCLUSIONS
  MCMV infection significantly increases atherosclerotic lesion area and aortic expression of atherogenic genes. These infection-induced effects indicate mechanisms by which cytomegalovirus may contribute to atherosclerotic disease initiation and progression and to the precipitation of clinical events. These results additionally add to data compatible with the concept that infection does play an important role in atherosclerotic disease.
authors.affiliation: Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC 20010, USA. mary.s.burnett-miller@medstar.net
authors.forename: Mary Susan
authors.initials: MS
authors.lastname: Burnett
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Durrani
authors.forename: Eugenio
authors.initials: E
authors.lastname: Stabile
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Saji
authors.forename: Cheol W
authors.initials: CW
authors.lastname: Lee
authors.forename: Tim D
authors.initials: TD
authors.lastname: Kinnaird
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D002791:Cholesterol, Dietary / Q000494:pharmacology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D002791:Cholesterol, Dietary; C485969:Cxcl9 protein, mouse; D007371:Interferon-gamma