Evaluation of new predictors of transplant vasculopathy in heart transplant recipients.

Cardiac allograft vasculopathy is the most important cause of death in heart transplant recipients. Both allo-immune and non-immune mechanisms play a role in the pathogenesis of transplant vasculopathy. Both allo-immune and non-immune factors induce endothelial dysfunction and endothelial injury that promote inflammation and smooth muscle cell proliferation in the coronary arteries of the graft. On the other hand, endothelial repair mechanisms may counteract these processes. Endothelial progenitor cells (EPCs) play a role in maintenance and repair of the integrity of the vascular endothelium. They may incorporate in the endothelium or promote reendothelialisation in a paracrine way. We have previously demonstrated that elevated HDL cholesterol following human apo A-I transfer results in an increase of the number of circulating EPCs, enhances EPC function, increases EPC incorporation and reendothelialisation in allografts, and inhibits development of transplant vasculopathy. The aim of this project is to evaluate whether endothelial cell death, analysed by quantification of the number of CD31+/Annexin V+ apoptotic micro particles, and endothelial repair mechanisms (using EPC number and function as parameters) correlate with angiographic transplant vasculopathy in a cross-sectional study and are predictive for progression of transplant vasculopathy evaluated by intravascular ultrasound in a prospective study. A third finality is to investigate HDL function and to analyse whether diverse parameters of HDL function correlate with or are predictive for transplant vasculopathy.

Keywords:High density lipoproteins, Endothelial progenitor cells, Endothelial repaiHeart transplantation, Transplant vasculopathy, Allograft vasculopathy

Disciplines:Cardiac and vascular medicine