691. Murine Cytomegalovirus (MCMV) Infection Is Associated with Early Progression of Atherosclerotic Lesions in Apo E Knockout Mice
Session: Abstracts: Virology
Friday, October 22, 2010
Background:

Atherosclerosis is a chronic multifactorial inflammatory disease of the vascular system and the major cause of morbidity and mortality in developed countries.  We previously reported that murine cytomegalovirus (MCMV) infection in Apo E knockout (KO) mice induced transcription of adhesion molecules (ICAM-1, VCAM-1 and MCP-1) and pro-inflammatory cytokines in hearts and aortas.  In this study we investigated if these molecular changes induced by  MCMV infection play a role in accelerating lesion progression to advanced stages earlier during atherogenesis. 

Methods:

Apo E KO mice were infected with a sublethal dose of MCMV.  At 2.5 and 4.5 months post-infection (p.i.), aortas were dissected and sections analyzed for lesion complexity and stage (Oil-red staining).  Chemokine and cytokine levels in aortas and sera were analyzed by real-time PCR and ELISA respectively, and cholesterol and triglycerides in sera were determined using standard methods.

Results:

MCMV-infection in Apo E KO mice was associated with advanced valvular and distal atherosclerotic lesions earlier, at 2.5 months p.i.  Lesions were ~2-fold and ~5-fold larger, respectively, in heart valves and distal areas of the aortas of infected compared to uninfected Apo E KO mice.  Valvular and aortic lesions of infected mice showed features of advanced disease including complex atheromas with intima fibrosis and possible rupture (stages V and VI)  compared to  initial fatty streaks with subintimal lipid accumulation typical of early stages (stage III)  in uninfected mice.  By 4.5 months p.i., appearance and staging of lesions in both groups of mice was comparable (stage V-VI).  In accord with lesion progression, levels of VCAM-1, ICAM-1 and MCP-1 were 6-fold and 4-fold (ICAM and MCP) higher, respectively, in aortas of infected than uninfected mice at 2.5 months p.i.  By 4.5 months, only VCAM levels remained elevated in infected mice. No differences in cholesterol and triglycerides levels were observed.  

Conclusion:

MCMV infection is associated with early progression of atherosclerosis to advanced stages in valvular and distal aortic areas.  The elevated production of pro-inflammatory molecules induced by the virus may be responsible for the progression and complexity of lesions at earlier times.


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Speakers:
Yajarayma J. Tang-Feldman, MA , Internal Medicine, University of California, Davis Health System, Davis, CA
Stephanie R. Lochhead, BS , Internal Medicine, University of California, Davis Health System, Davis, CA
G. Raymond Lochhead, BS , Internal Medicine, University of California, Davis Health System, Davis, CA
Cindy Q. Yu, MD , Pathology, University of California, Davis Health System, Sacramento, CA
Claire Pomeroy, MD , Internal Medicine, University of California, Davis Health System, Sacramento, CA

Disclosures:

Y. J. Tang-Feldman, None

S. R. Lochhead, None

G. R. Lochhead, None

C. Q. Yu, None

C. Pomeroy, None

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