This Article Full Text Full Text (PDF) All Versions of this Article: 109/7/893    most recent 01.CIR.0000112585.47513.45v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burnett, M. S. Articles by Epstein, S. E. Search for Related Content PubMed PubMed Citation Articles by Burnett, M. S. Articles by Epstein, S. E. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Cytomegalovirus Infections Related Collections Gene expression Mechanism of atherosclerosis/growth factors

(Circulation. 2004;109:893-897.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Murine Cytomegalovirus Infection Increases Aortic Expression of Proatherosclerotic Genes

Mary Susan Burnett, PhD; Sarfraz Durrani, MD; Eugenio Stabile, MD; Motoyasu Saji, MD, PhD; Cheol W. Lee, MD; Tim D. Kinnaird, MD; Eric P. Hoffman, PhD; Stephen E. Epstein, MD

From the Cardiovascular Research Institute (M.S.B., E.S., C.W.L., T.D.K., S.E.E.), MedStar Research Institute, Washington Hospital Center; Research Center for Genetic Medicine (S.D., E.P.H.), Children’s National Medical Center; and MedStar Research Institute (M.S.), Washington Hospital Center, Washington, DC.

Correspondence to Mary Susan Burnett, Cardiovascular Research Institute, 110 Irving St, NW, Suite 4B-1, Washington, DC 20010. E-mail mary.s.burnett-miller{at}medstar.net

Received March 6, 2003; de novo received August 12, 2003; revision received October 15, 2003; accepted October 19, 2003.

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.

Methods and 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-, and interferon- 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.

Key Words: atherosclerosis • infection • genes

This article has been cited by other articles:

				S. E. Epstein, J. Zhu, A. H. Najafi, and M. S. Burnett Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture Circulation, June 23, 2009; 119(24): 3133 - 3141. [Full Text] [PDF]

				R. B. Gombos, V. Wolan, K. McDonald, and D. G. Hemmings Impaired vascular function in mice with an active cytomegalovirus infection Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H937 - H945. [Abstract] [Full Text] [PDF]

				J. L. Stern and B. Slobedman Human Cytomegalovirus Latent Infection of Myeloid Cells Directs Monocyte Migration by Up-Regulating Monocyte Chemotactic Protein-1 J. Immunol., May 15, 2008; 180(10): 6577 - 6585. [Abstract] [Full Text] [PDF]

				X. Yang, V. Murthy, K. Schultz, J. B. Tatro, K. A. Fitzgerald, and D. Beasley Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2334 - H2343. [Abstract] [Full Text] [PDF]

				A.P.J.J. Bijnens, E. Lutgens, T. Ayoubi, J. Kuiper, A.J. Horrevoets, and M.J.A.P. Daemen Genome-Wide Expression Studies of Atherosclerosis: Critical Issues in Methodology, Analysis, Interpretation of Transcriptomics Data Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1226 - 1235. [Abstract] [Full Text] [PDF]

				A. C. Kalil, J. Levitsky, E. Lyden, J. Stoner, and A. G. Freifeld Meta-Analysis: The Efficacy of Strategies To Prevent Organ Disease by Cytomegalovirus in Solid Organ Transplant Recipients Ann Intern Med, December 20, 2005; 143(12): 870 - 880. [Abstract] [Full Text] [PDF]

				S.-P. Gravel and M. J. Servant Roles of an I{kappa}B Kinase-related Pathway in Human Cytomegalovirus-infected Vascular Smooth Muscle Cells: A MOLECULAR LINK IN PATHOGEN-INDUCED PROATHEROSCLEROTIC CONDITIONS J. Biol. Chem., March 4, 2005; 280(9): 7477 - 7486. [Abstract] [Full Text] [PDF]

				K. S. Michelsen, T. M. Doherty, P. K. Shah, and M. Arditi TLR Signaling: An Emerging Bridge from Innate Immunity to Atherogenesis J. Immunol., November 15, 2004; 173(10): 5901 - 5907. [Abstract] [Full Text] [PDF]

				S. E. Epstein, E. Stabile, T. Kinnaird, C. W. Lee, L. Clavijo, and M. S. Burnett Janus Phenomenon: The Interrelated Tradeoffs Inherent in Therapies Designed to Enhance Collateral Formation and Those Designed to Inhibit Atherogenesis Circulation, June 15, 2004; 109(23): 2826 - 2831. [Full Text] [PDF]