The Paradox of Donor Stimulation of Endothelial-induced Smooth Muscle Growth

Cardiac allograft vasculopathy (CAV) is the major cause of long-term morbidity and mortality in cardiac transplant recipients. It appears to be related to immune damage to the coronary endothelial cells, resulting in intimal proliferation. In order to delineate the mechanisms by which CAV can occur, co-culture model of human endothelial cells (EC) and smooth muscle cells (SMC) obtained from the donor at the time of organ procurement was utilized. These cells were separated by collagenase digestion, and cultured for four passages. EC and SMC were then grown to confluence in the separate chambers of co-culture plate separated by 0.45 micron Millipore filter. Preserved lymphocytes (LYMPH) obtained from the donor and pooled blood lymphocytes from the recipient 3-4 weeks following transplant were added to the EC well so as to cause an immunologic stimulation of the EC. None of the recipients were exposed to monoclonal or polyclonal antibodies to lymphocytes. All cultures and assays were done in triplicate. Results are as follows: The donor EC/donor LYMPH co-culture stimulated SMC growth measured by H3 thymidine incorporation in 4 of 5 patients. The donor EC/recipient LYMPH co-culture did not result in significant SMC H3 thymidine incorporation. Conclusion: These paradoxical findings of lack in significant SMC proliferation in the recipient stimulated donor cells continue to raise questions in relation to the effects of circulating lymphocytes on the development of cardiac allograft vasculopathy.