This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary goals of this study are to measure HCMV activation and viral gene products, host immune responses, and the eNOS pathway, during progression to transplant arteriosclerosis (TA). Longitudinal measures of each of these consequences of CMV infection will be correlated with development of TA over time. For comparison, these longitudinal studies will be conducted in patients without HCMV infection, primary infection, reactivation, and latently-infected blood donors. Simultaneous blood and EMB samples will allow comparisons to be made between the two types of samples regarding markers of CMV infection. CMV-specific immune responses will be determined by evaluating MHC class I and class II restricted responses of lymphocytes in peripheral blood and by in situ examination of EMB in Project 1. Blood and EMB samples will be cultured for CMV, and CMV isolates from patients will be used for characterization CMV genotype, chemokines and chemokine receptors, and cytokines in Project 2, and for studies of their effects on the eNOS pathway in endothelial cell culture systems in Project 3. The correlation of CMV activation, genotype and CMV gene products with host adaptive immune response and TA, will provide a core understanding of the pathogenesis of this disease as well a direct understanding of inflammatory processes in arteriosclerosis, whether CMV-mediated or not. First time heart transplant recipients have been easily enrolled in this diagnostic and sampling study. Patients enrolled come through the GCRC when they are scheduled for their baseline arteriogram and intravascular ultrasound within 4-6 weeks after transplant. The samples retrieved, an average of 6-8 per week, from the routine heart biopsies and blood work are accessioned and catalogued through the labeling, and database system created for the study and administered through the GCRC.
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