Cardiac allograft vasculopathy: Microvascular arteriolar capillaries ('capioles") and survival

Abstract

Cardiac allograft vasculopathy (CAV) is a serious complication of heart transplantation in adults and children. Risk factors include human leukocyte antigen mismatches, number and duration of rejection episodes, type of immunosuppression, antibody-mediated rejection, hypertension, hyperlipidemia, obesity, smoking, diabetes, cytomegalovirus infection, mode of donor brain death, donor age and ischemia/reperfusion injury. Endothelial injury and dysfunction in CAV are characterized by changes in adhesion molecules and up-regulation of major histocompatibility class II antigens followed by endothelial activation of complement C4d. Subsequently, activation of the coagulation cascade leads to deposition of fibrin on endothelium followed by proliferation and migration of vascular smooth muscle cells. The development of a special type of microvessels with phenotypic characteristics of arterial capillaries ("capioles") seems to provide a survival advantage for patients with CAV. Novel therapies of CAV include statins, and heparin-induced extracorporeal low-density lipoprotein apheresis. B beta15-42 which is a fibrin peptide has been shown to improve the graft microvasculature and to reduce ischemia/reperfusion-induced damage. Despite these advances, there is a need to identify and stratify individual CAV risk factors, to develop early biomarkers of CAV, and to better decipher the events that lead to antibody-mediated rejection.