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Circulation Research. 2001
Published online before print October 25, 2001, doi: 10.1161/hh2401.100601
A more recent version of this article appeared on December 7, 2001
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Submitted on November 27, 2000
Revised on October 12, 2001
Accepted on October 12, 2001

Cytomegalovirus Infection Accelerates Inflammation in Vascular Tissue Overexpressing Monocyte Chemoattractant Protein-1

M. Kent Froberg *, Alice Adams , Nicole Seacotte , Jan Parker-Thornburg , and Pappachan Kolattukudy

From the Departments of Pathology and Laboratory Medicine (M.K.F., N.S.) and Medical Microbiology and Immunology (M.K.F., A.A.), University of Minnesota-Duluth, School of Medicine, Duluth, Minn; and the NeuroBiotechnology Center (J.P.-T., P.K.), Ohio State University, Columbus, Ohio.

* To whom correspondence should be addressed. E-mail: kfroberg{at}d.umn.edu.

Cardiovascular disease is the leading cause of mortality in the United States. Atherosclerosis is responsible for most of this pathology and is an inflammatory disease with multiple cytokines and adhesion molecules expressed during atherogenesis. Cytomegalovirus (CMV), monocytes, and monocyte chemoattractant protein-1 (MCP-1) have all been implicated in human atherogenesis. A transgenic mouse overexpressing MCP-1 in the myocardium and pulmonary arteries develops myocarditis and pulmonary vascular inflammation. We infected MCP-1 transgenic mice with a sublethal dose of murine cytomegalovirus (MCMV) to look for evidence of accelerated inflammation in vascular tissues overexpressing MCP-1 to determine if MCMV could interact with monocytes and MCP-1 in a manner similar to what may occur in atherogenesis. MCMV infection of MCP-1 transgenic mice caused ascites, myocarditis, and pulmonary artery inflammation, which was not present in mock-infected MCP-1 or MCMV-infected wild-type mice. Inflammatory infiltrates in these tissues consisted of macrophages and T lymphocytes similar to the infiltrates seen in atherosclerosis. Virus presence in inflamed tissues was demonstrated by infecting transgenic mice with MCMV recombinant virus containing the gene sequence for the enhanced green fluorescent protein (EGFP). Human CMV could be involved in atherogenesis in a similar manner by interacting with monocytes and MCP-1 specifically expressed in vascular walls.


Key words: cytomegalovirus • atherosclerosis • monocyte chemoattractant protein-1 • monocytes




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