Vascular anticoagulation and transplant coronary artery disease

Fibrin deposits are found in and around the vessels in transplant coronary artery disease, in spontaneous atherosclerosis, and in the microvasculature of failing cardiac allografts. Fibrin is deposited due to a failure in ant icoagulant pathways, one of the most important being the heparan sulfate pr oteoglycan-antithrombin (AT) natural anticoagulant pathway. A failure in th is pathway results in a loss of AT binding in veins and arteries and increa sed fibrin deposition. This is associated with an increased risk of coronar y artery disease and graft failure. Recovery of the previously lost vascula r AT binding is associated with the development of a novel binding of AT by capillaries. The development of capillary AT binding is associated with si gnificantly less coronary artery disease and improved survival. Understandi ng the mechanisms involved in the development of this unusual binding of AT by capillaries is important in developing new treatments directed to promo te microvascular AT binding and reduce the deposition of fibrin.