Microvascular prothrombogenicity and transplant coronary artery disease.
A major impediment for the long-term success of heart transplantation is the development of transplant coronary artery disease (CAD). Several risk factors for the development of transplant CAD are associated with the transformation of a normal thromboresistant microvasculature into a prothrombogenic microvasculature. Prothrombogenicity is characterized by loss of anticoagulation (i.e. loss of antithrombin), loss of fibrinolytic activity (i.e., loss of tissue plasminogen activator) and presence of endothelial activation (i.e. upregulation of endothelial intercellular adhesion molecule-1 and major histocompatibility class II antigen human leukocyte antigen-DR) in the arterial allograft microvasculature. Microvascular prothrombogenicity during the first trimester after transplantation is directly associated with subsequent development of transplant CAD. Although the mechanisms responsible for the loss of thromboresistant endothelium are unclear, the fact that changes in the anticoagulant, fibrinolytic, and activational status of endothelial cells may occur early after transplantation suggests a peritransplant phenomenon as an initiating event. Reducing prothrombogenicity of the cardiac microvasculature early after transplantation could slow the development of transplant CAD and significantly improve allograft survival.
Labarrere
Carlos A
CA
Methodist Research Institute at Clarian Health, Indianapolis, IN 46202, USA. clabarrere@clarian.org
Deng
Mario C
MC
D000818:Animals; D003327:Coronary Disease / Q000209:etiology*; D003328:Coronary Thrombosis / Q000209:etiology*; D004730:Endothelium, Vascular / Q000166:cytology; D006085:Graft Survival; D006684:HLA-DR Antigens / Q000032:analysis; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008833:Microcirculation; D010959:Tissue Plasminogen Activator / Q000097:blood; D014184:Transplantation, Homologous
D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D010959:Tissue Plasminogen Activator