CYTOMEGALOVIRUS-INFECTION ENHANCES MESSENGER-RNA EXPRESSION OF PLATELET-DERIVED GROWTH FACTOR-BB AND TRANSFORMING GROWTH FACTOR-BETA(1) IN RAT AORTIC ALLOGRAFTS - POSSIBLE MECHANISM FOR CYTOMEGALOVIRUS-ENHANCED GRAFT ARTERIOSCLEROSIS

We have recently demonstrated that rat cytomegalovirus (RCMV) infectio n induces an early inflammatory response in the adventitia (perivascul itis) and in the subendothelial space (endothelialitis) as well as dou bles smooth muscle cell (SMC) proliferation and intimal thickening of rat aortic allografts performed from the DA (AG-B4, RT1(a)) to the WF (AG-B2, RT1(v)) strain. In this study, the impact of RCMV infection on the structure of inflammation in the allograft adventitia and on the expression of SMC growth factors in the allograft vascular wall was in vestigated. The recipient rats were inoculated with 10(5) plaque-formi ng U of RCMV Maastricht strain or left noninfected and used as control s. The allografts were removed at 7 days and 1 and 3 months after tran splantation and processed for morphometry and immunohistochemistry. RN A was isolated for reverse transcriptase polymerase chain reaction (RT -PCR). RCMV infection was associated with significantly upregulated pr esence (P<.05) of T helper (W3/25), T cytotoxic (OX8), and natural kil ler (3.2.3) cells in the allograft adventitia 7 days after transplanta tion but not thereafter. More monocyte/macrophages (OX42) were also pr esent in RCMV-infected allografts, but the difference was not signific ant. Concomitantly, RCMV infection significantly enhanced (P<.05) the expression of major histocompatibility complex class II (OX6) and almo st doubled (P=NS) the expression of interleukin-2R (CD25), intercellul ar adhesion molecule-1 (CD54;1A29), and lymphocyte function-associated antigen-1 alpha-chain (CD11a; WT.1) in the adventitial inflammatory i nfiltrate. RCMV infection was linked with an early, prominent expressi on of both PDGF-BB mRNA at 7 days (P<.05) and at 1 month (P<.025) and of transforming growth factor-beta(1) mRNA at 7 days (P<.025) and at 1 month (P<.025) after transplantation. A less-prominent mRNA upregulat ion of acidic fibroblast growth factor (P<.05) was associated with RCM V infection at 7 days and at 1 month, as well as of epidermal growth f actor at 1 month after transplantation, when compared with noninfected allografts, although the mRNA expression in both groups was below the levels of nontransplanted DA aortas. RCMV infection almost doubled ba sic fibroblast growth factor mRNA expression (P=NS) in the allograft v ascular wall at 7 days and at 1 month. RCMV infection had no additiona l impact on insulin-like growth factor-1 mRNA expression when compared with noninfected allografts. Our results suggest that RCMV infection- induced early inflammatory response in the Vascular wall is linked wit h an early activation of the inflammatory cells and enhanced mRNA expr ession of PDGF-BB and transforming growth factor-beta(1). We suggest t hat these biochemical responses may play a role in the generation of R CMV-enhanced allograft arteriosclerosis.