This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nerheim, P. L. Articles by Weintraub, N. L. Search for Related Content PubMed PubMed Citation Articles by Nerheim, P. L. Articles by Weintraub, N. L.

(American Journal of Pathology. 2004;164:589-600.)
© 2004 American Society for Investigative Pathology

Enhanced Cytomegalovirus Infection in Atherosclerotic Human Blood Vessels

Pamela L. Nerheim^*, Jeffery L. Meier^*, Mohammad A. Vasef, Wei-Gen Li^*, Ling Hu^*, James B. Rice^*, Daniel Gavrila^*, Wayne E. Richenbacher^¶ and Neal L. Weintraub^*

From the Departments of Internal Medicine,^* Pathology, Biochemistry, and Surgery,^¶ University of Iowa College of Medicine, Iowa City; and the Veterans Administration Medical Center, Iowa City, Iowa

Human cytomegalovirus (CMV) is a possible co-factor in atherogenesis and vascular occlusion, but its ability to actively infect medium and large blood vessels is unclear. A vascular explant model was adapted to investigate CMV infection in human coronary artery, internal mammary artery (IMA), and saphenous vein (SV). Vascular explants were inoculated with CMV Towne or low-passage clinical isolate and examined in situ for CMV cytopathic effect and immediate-early and early antigens, as indicators of active infection. At 5 to 7 days after inoculation, we found that CMV Towne actively infected eight of eight different atherosclerotic blood vessel explants (coronary artery, n = 4; SV and IMA grafts, n = 4), whereas it only infected 2 of 14 nonatherosclerotic blood vessel explants (SV, n = 10; IMA, n = 4) (P = 0.001). The CMV clinical isolate actively infected none of six sets of nonatherosclerotic SV explants at 5 to 7 days after inoculation. The active CMV infections involved adventitial and, less frequently, intimal cells. A small subset of infected cells in atherosclerotic tissue expresses the endothelial cell marker CD31. Smooth muscle cells residing in both atherosclerotic and nonatherosclerotic blood vessels were free of active CMV infections even after all vascular tissue layers were exposed to the virus. In contrast, active CMV Towne infection was evident at 2 days after inoculation in smooth muscle cells and endothelial cells previously isolated from the SV tissues. We conclude that active CMV infection is enhanced in atherosclerotic blood vessels compared to atherosclerosis-free vascular equivalents, and this viral activity is restricted to subpopulations of intimal and adventitial cells.

This article has been cited by other articles:

				Y. H. Shen, L. Zhang, B. Utama, J. Wang, Y. Gan, X. Wang, J. Wang, L. Chen, G. M. Vercellotti, J. S. Coselli, et al. Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10) Cardiovasc Res, February 1, 2006; 69(2): 502 - 511. [Abstract] [Full Text] [PDF]

				G. Almanzar, S. Schwaiger, B. Jenewein, M. Keller, D. Herndler-Brandstetter, R. Wurzner, D. Schonitzer, and B. Grubeck-Loebenstein Long-Term Cytomegalovirus Infection Leads to Significant Changes in the Composition of the CD8+ T-Cell Repertoire, Which May Be the Basis for an Imbalance in the Cytokine Production Profile in Elderly Persons J. Virol., March 15, 2005; 79(6): 3675 - 3683. [Abstract] [Full Text] [PDF]

				C. Kupatt, C. Dessy, R. Hinkel, P. Raake, G. Daneau, C. Bouzin, P. Boekstegers, and O. Feron Heat Shock Protein 90 Transfection Reduces Ischemia-Reperfusion-Induced Myocardial Dysfunction via Reciprocal Endothelial NO Synthase Serine 1177 Phosphorylation and Threonine 495 Dephosphorylation Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1435 - 1441. [Abstract] [Full Text] [PDF]