NEOINTIMAL SMOOTH-MUSCLE CELL PHENOTYPE IS IMPORTANT IN ITS SUSCEPTIBILITY TO CYTOMEGALOVIRUS (CMV) INFECTION - A STUDY IN RAT

Objective: Recently, we have found that rat CMV (RCMV) infected smooth muscle cells (SMCs) in rat carotid arteries when administered 14 days after balloon injury. In the present study we investigated (1) the lo ng term effects of CMV infection on neointimal cross-sectional area, a nd (2) whether the phenotype of the intimal SMCs influences their susc eptibility to active CMV infection. Methods: In the first part of the study, rats received RCMV intravenously, two weeks after balloon cathe terisation of the left carotid artery and were sacrificed twenty weeks after catheterisation. Continuous BrdU infusion was performed by subc utaneously implanted osmotic pumps during the last two weeks of life. In the second part RCMV was administered eight weeks after catheterisa tion and rats were sacrificed two weeks later. Immunohistochemistry wa s used to detect viral antigens, to determine BrdU incorporation as we ll as the contents of alpha-actin, desmin and vimentin in the carotid arteries. Intima and media cross-sectional areas were determined using computerized morphometry. Results and conclusions: RCMV infection did not induce any differences in intima or media cross-sectional areas o f the injured carotid artery, nor in the extent of SMC proliferation a s shown by BrdU incorporation, 20 weeks after balloon catheterisation. Eight weeks after balloon catheterisation, RCMV no longer infected ne ointimal SMCs. This non-responsiveness to RCMV was associated with 're -differentiation' of the eight weeks old neointima, compared with two weeks after catheterization, as shown by the contents of alpha-actin, desmin and vimentin. Our data suggest that intimal SMC phenotype deter mines its susceptibility to active RCMV infection in vivo. Since de-di fferentiation of neointimal SMCs is associated with enhanced prolifera tion of these cells it is stated that de-differentiation or proliferat ion is prerequisite for infection. (C) 1997 Elsevier Science B.V.