Benefits of proliferation signal inhibitors beyond immunosuppression. Vascular protection and experience in heart transplantation

Proliferation Signal inhibitors (PSI), sirolimus and everolimus, possess immunosuppressive and antiproliferative properties that have a substantial impact in organ transplantation. Their anti proliferative and pro-apoptotic action on vascular smooth muscle cells and endothelial cells, with positive effects on vascular remodeling, intimal proliferation, and atheroma plaques, has been demonstrated in many experimental studies in cell culture and on animal vascular, cardiac, and renal models. In humans, the PSI show a major advantage in heart transplantation, since they contribute satisfactory immunosuppression white preventing coronary vasculopathy related to intimal proliferation of smooth muscle cells, a factor that limits the tong-term success of the graft. Intravascular ultrasound explorations, which measure intima thickness, showed that PIS treatment can inhibit intracoronary intimal proliferation after heart transplantation and thus reduce the morbidity and mortality at the medium term in transplantation patients. In kidney transplantation, even though their impact is less clear for the moment because of the multifactorial aspect of chronic graft dysfunction, the PSI nevertheless contribute undeniable benefits in terms of improving renal function and reducing the histological lesions of chronic allograft nephropathy. (C) 2009 Elsevier Masson SAS et Association Societe de Nephrologie. All rights reserved.