CMV and transplant-related coronary atherosclerosis: An immunohistochemical, in situ hybridization, and polymerase chain reaction in situ study

Accelerated graft coronary atherosclerosis is the main obstacle to long-ter m survival in patients who have had a heart transplant. A possible involvem ent of the human cytomegalovirus (HCMV) in this type of coronary atheroscle rosis has been postulated by many authors but has not been definitively dem onstrated. In an attempt to clarify the role of HCMV infection in the patho genesis of this complication, we looked for in situ antigens or DNA of HCMV in 30 coronary artery segments obtained at necropsy from patients who had undergone orthotopic cardiac transplantation at the Sao Paulo Heart Institu te. We tried to correlate these HCMV markers with the presence of inflammat ion and/or atherosclerosis in histologic sections. The patients were groupe d as follows: GI, less than 170 days of graft survival and absent/mild athe rosclerosis; GII, more than 170 days of graft survival and absent/mild athe rosclerosis; GIII, more than 170 days of graft survival and severe/moderate atherosclerosis (170 days was the shortest graft survival time associated with atherosclerosis). The search for HCMV genome and antigens in the coron ary artery sections was performed using immunohistochemistry, in situ hybri dization, and polymerase chain reaction in situ techniques. Immunohistochem istry and in situ hybridization revealed no evidence of HCMV in all 30 case s. Polymerase chain reaction in situ revealed scarce HCMV-positive lymphocy tes in two cases tone each from GI and GIII) located in the adventitial lay er. These findings preclude a direct role for the HCMV in the pathogenesis of accelerated graft coronary;atherosclerosis. However, the possibility of an indirect effect of the virus, such as an immune-mediated inflammatory re sponse by the host that increases the expression of histocompatibility anti gens, leading to tissue injury, cannot be excluded.