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 anticoagulant pathways, one of the most important being the heparan sulfate proteoglycan-antithrombin (AT) natural anticoagulant pathway. A failure in this pathway results in a loss of AT binding in veins and arteries and increased fibrin deposition. This is associated with an increased risk of coronary artery disease and graft failure. Recovery of the previously lost vascular AT binding is associated with the development of a novel binding of AT by capillaries. The development of capillary AT binding is associated with significantly less coronary artery disease and improved survival. Understanding the mechanisms involved in the development of this unusual binding of AT by capillaries is important in developing new treatments directed to promote microvascular AT binding and reduce the deposition of fibrin.
Labarrere
C A
CA
Methodist Research Institute, Clarian Health Partners, 1812 N. Capitol Avenue, Indianapolis, IN 46202, USA.
Abellada
G C
GC
D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation; D002196:Capillaries / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D012306:Risk; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000378:metabolism
D000991:Antithrombins; D019812:Heparan Sulfate Proteoglycans; D005337:Fibrin