Modified endothelial cells in graft vasculopathy

Abstract

Occlusion of venous bypass grafts after coronary revascularization grafting represents the main reason for re-do operations. Arterial pressure as well as mechanical injury of the venous wall lead to endothelial dysfunction, causing intimal hyperplasia with luminal stenosis and eventually occlusion. In the transplanted heart, coronary artery disease limits the long-term success of cardiac transplantation. The disease is characterized by the interaction of activated immunologic cells and donor epicardical and microvascular endothelium. The ex vivo modification of endothelial cells may offer a therapeutic option to overcome both kinds of graft vasculopathy. Seeding of human endothelial cells on artificial and bioartificial acellularized vessel matrices has proven possible. The use of xenogenic matrices initially acellularized and recellularized with autologic endothelial cells and myofibroblasts may help to overcome the lack of vascular and valvular grafts with long durability. In addition, gene therapeutic methods to modify the function of such endothelial cells may offer a new therapeutic strategy, such as over-expression of nitric monoxide or inhibition of matrix metalloprotinases. First results of large animal studies show promising results and may lead to the first clinical trials in the near future.