The endothelium in clinical cardiac transplantation

Cardiac transplantation is the most successful therapy for refractory heart failure, but clinical transplantation is still confronted with the problems of acute rejection and acute pump failure. The limiting factor in achieving prolonged survival remains cardiac allograft vasculopathy. In recent years it has become apparent that from brain death onward, the cardiac endothelium plays a key role in these acute and chronic events. Brain death is associated with an inflammatory response that primes the endothelium for cumulative injury during the subsequent stages of ischemic cold storage, reperfusion and allorecognition. As a structural and functional interface, the endothelium is the site at which inflammatory cells move from the bloodstream through the vessel wall into the parenchyma. The endothelium interacts with the complement system, the coagulation and inflammatory cascades, circulating leukocytes, the immune system, the smooth muscle in the vessel wall, and the surrounding matrix and cardiomyocytes. A better understanding of its many roles may lead to expansion of our therapeutic possibilities and better outcomes overall. This article reviews the possible roles of the endothelium in relation to cardiac transplantation, and discusses the diagnostic and therapeutic modalities that are available to date.