title: Murine cytomegalovirus (MCMV) infection upregulates P38 MAP kinase in aortas of Apo E KO mice: a molecular mechanism for MCMV-induced acceleration of atherosclerosis.
abstract: Multiple studies suggest an association between cytomegalovirus (CMV) infection and atherogenesis; however, the molecular mechanisms by which viral infection might exacerbate atherosclerosis are not well understood. Aortas of MCMV-infected and uninfected Apo E knockout (KO) mice were analyzed for atherosclerotic lesion development and differential gene expression. Lesions in the infected mice were larger and showed more advanced disease compared to the uninfected mice. Sixty percent of the genes in the MAPK pathway were upregulated in the infected mice. p38 and ERK 1/2 MAPK genes were 5.6- and 2.0-fold higher, respectively, in aortas of infected vs. uninfected mice. Levels of VCAM-1, ICAM-1, and MCP-1 were ~2.0-2.6-fold higher in aortas of infected vs. uninfected mice. Inhibition of p38 with SB203580 resulted in lower levels of pro-atherogenic molecules and MCMV viral load in aortas of infected mice. MCMV-induced upregulation of p38 may drive the virus-induced acceleration of atherogenesis observed in our model.
authors.affiliation: Department of Internal Medicine, University of California, Davis, Sacramento, CA 95817, USA. yjtangfeldman@ucdavis.edu
authors.forename: Yajarayma J
authors.initials: YJ
authors.lastname: Tang-Feldman
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Lochhead
authors.forename: G Raymond
authors.initials: GR
authors.lastname: Lochhead
authors.forename: Cindy
authors.initials: C
authors.lastname: Yu
authors.forename: Michael
authors.initials: M
authors.lastname: George
authors.forename: Amparo C
authors.initials: AC
authors.lastname: Villablanca
authors.forename: Claire
authors.initials: C
authors.lastname: Pomeroy
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000821:virology*; D001018:Aortic Diseases / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006566:Herpesviridae Infections / Q000150:complications / Q000235:genetics / Q000821:virology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018146:Muromegalovirus / Q000472:pathogenicity*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C090509:Icam1 protein, mouse; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases