Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E-deficient mouse

被引:84
作者
Alber, DG
Powell, KL
Vallance, P
Goodwin, DA
Grahame-Clarke, C
机构
[1] UCL, Wolfson Inst Biomed Res, London WC1E 6AU, England
[2] UCL, Ctr Clin Pharmacol & Therapeut, London WC1E 6AU, England
关键词
infection; atherosclerosis; viruses; apolipoproteins; pathology;
D O I
10.1161/01.CIR.102.7.779
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Human herpesviruses have been implicated but not proven to be involved in the etiology of atherosclerosis. To determine whether there is a causal relationship, the effect of herpesvirus infection on the development of atherosclerosis was assessed in the apolipoprotein E-deficient (apoE-/-) mouse. Methods and Results-In the present study, 3- to 4-week-old apoE-/- mice were infected with murine gamma-herpesvirus-68 (MHV-68), Atheroma formation was accelerated over a 24-week period in infected apoE-/- mice compared with control uninfected apoE-/- mice. Acceleration of atherosclerosis was reduced by antiviral drug administration. Histological analysis of the atheromatous plaques showed no difference between lesions of infected and control mice. Viral mRNA was present ill the aortas of infected mice before lesion development on day 5 after infection. This suggests that the virus may initiate endothelial injury, which is believed to be an early event in the development of atherosclerosis. Therefore, the virus may play a direct role in atherosclerosis rather than be an "innocent bystander." Conclusions These data demonstrate that a gamma-herpesvirus can accelerate atherosclerosis in the apoE-/- mouse. This study provides the first report of a murine model in which to study the causative role of herpesvirus infection in the development of atherosclerosis.
引用
收藏
页码:779 / 785
页数:7
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