Prothrombogenic microvasculature and transplant outcome

Carlos A. Labarrere, David R. Nelson, Steven J. Miller

Research output: Contribution to journalReview article

Abstract

A major obstacle to the long-term success of transplanted solid organs is the development of transplant-associated vasculopathy. A prime risk factor for the development of vascular disease is the conversion of the microvasculature from a thromboresistant to a prothrombogenic state, leading to fibrin deposition. A thromboresistant microvasculature is characterized by vessels in which the endothelium has intact natural anticoagulant and fibrinolytic pathways and by the lack of activated endothelial cells. A prothrombogenic microvasculature results when there are failures in anticoagulant pathways, such as the protein C and the vascular antithrombin pathways, or when there is an absence of fibrinolytic activity, as when tissue plasminogen activator is depleted. Activated endothelium, characterized by increased arterial expression of moieties such as intercellular adhesion molecule-1 and human leukocyte antigen-DR, also is associated with a prothrombogenic microvasculature. The presence of a prothrombogenic microvasculature early after transplantation is associated with an increased incidence of both coronary artery disease and chronic graft failure. 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. The use of both new and established therapies to inhibit the formation of a prothrombogenic microvasculature could slow the development of transplant coronary artery disease and significantly improve allograft survival.

Original languageEnglish (US)
Pages (from-to)212-222
Number of pages11
JournalGraft
Volume5
Issue number4
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Transplantation

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