Heart allograft endothelial cell dysfunction. Cause, course, and consequences.

Abstract

Allograft coronary endothelial cells can serve as potent stimulators (antigen-presenting cells) as well as targets of allogeneic lymphocyte reactivity. Independent of the cause leading to endothelial cell injury after transplantation, endothelial cell activation and dysfunction occurs, associated with modification in endothelial cell-dependent molecule expression. The prevalence of coronary endothelial vasomotor dysfunction is approximately 20-30% during the first year, and 30-40% in the long-term follow-up. Importantly, no association is detectable between endothelial dysfunction and intimal thickness, suggesting two distinct entities of allograft vasculopathy. Early predictors of vasomotor dysfunction are proinflammatory cytokines and endothelin expression. Repetitive subendocardial ischemia during myocardial stress (due to microvascular dysfunction) may result in an impairment of left ventricular function. In non-transplant patients coronary endothelial dysfunction predicts cardiac events during long-term follow-up. It is reasonable that early administration of endothelial-protective compounds is necessary for protection of allograft endothelial dysfunction and vasculopathy during follow-up. The explanted donor heart may offer a potential for gene therapy techniques including modification of allograft phenotype and modulation of the host alloimmune response. Other protective strategies may include improvement of cardioplegic solutions and reperfusion strategies, recovery of the imbalance between vasoactive mediators, and treatment with HMG-CoA-reductase inhibitors and/or ACE inhibitors.