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Effects of MF-tricyclic, a selective cyclooxygenase-2 inhibitor, on atherosclerosis progression and susceptibility to cytomegalovirus replication in apolipoprotein-E knockout mice

^* Cardiovascular Research Institute, Medstar Research Institute, Washington Hospital Center, Washington, DC, USA

View larger version (10K): [in a new window]   Figure 1 Mouse cytomegalovirus (CMV) deoxyribonucleic acid (DNA) concentration in mouse salivary glands. This value (which underwent square root transformation before statistical analysis) was taken as a polymerase chain reaction (PCR)-derived index of the number of viral particles present in the tissue. The results show a dose-response curve, with highest drug level associated with highest viral load. All sham-infected mice were negative for CMV DNA. The gene targeted for PCR amplification was mouse CMV IE1 exon 4. *p = 0.05 vs. no drug treatment group.

View larger version (11K): [in a new window]   Figure 2 Anti-mouse cytomegalovirus (CMV) immunoglobulin G (IgG) antibody titer in mice sera. All mice were infected with the same concentration of virus. Cytomegalovirus antibody titers increased with increasing dose of the cyclooxygenase-2 inhibitor, compatible with a drug-induced increase in viral load seen in Figure 1. All sham-infected mice were negative for anti-CMV IgG antibodies. *p = 0.025 vs. no drug treatment group; **p = 0.015 vs. no drug treatment group.

View larger version (12K): [in a new window]   Figure 3 Atherosclerotic lesion area. Selective cyclooxygenase-2 inhibition consistently increased lesion size: by 84% in the noninfected group, and by 70% and by 80% in the cytomegalovirus (CMV)-infected low-dose and high-dose groups respectively. In this study, infection with CMV did not increase lesion size. *p = 0.013 vs. no drug treatment/no inoculum group; #p < 0.01 vs. no drug treatment/no inoculum group; p < 0.01 vs. no drug treatment/sham infection group; &p = 0.02 vs. no drug treatment group/CMV infection group; p = 0.05 vs. no drug treatment group/CMV infection group.

View larger version (76K): [in a new window]   Figure 4 Oil red O staining of atherosclerotic lesions in the aorta. Representative photomicrographs (x10 magnification) of the lesions present in two uninfected mice. (A) Untreated with MF-tricyclic; (B) treated with MF-tricyclic, 12 mg/kg/day. The arrows point to some of the aortic valve leaflets, indicating that the sections employed for measuring lesion size are located, as is traditional, at the root of the aorta.