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(Circulation Research. 2003;92:12.)
© 2003 American Heart Association, Inc.

Editorials

Thrombosis of Vein Grafts

Wall Tension Restrains Thrombomodulin Expression

Steven R. Lentz

From the Department of Internal Medicine, University of Iowa, and Veterans Affairs Medical Center, Iowa City, Iowa.

Correspondence to Steven R. Lentz, MD, PhD, Dept of Internal Medicine, C303 GH, The University of Iowa, Iowa City, IA 52242. E-mail steven-lentz@uiowa.edu

Key Words: endothelium • thrombin • thrombomodulin • vein graft • strain

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Thrombosis is a major complication leading to early vein graft failure in patients undergoing coronary artery bypass surgery.¹ Like thrombosis at other sites, thrombosis of vein grafts results from a failure of hemostatic balance, which is normally maintained by a complex series of coagulation reactions that involve both systemic and local factors.² The endothelium contributes to local hemostatic balance by producing thrombomodulin, which functions as an essential cofactor for the activation of anticoagulant protein C³ and other antithrombotic molecules such as heparin sulfates, plasminogen activators, and nitric oxide. The antithrombotic properties of endothelium may become compromised when vein grafts are exposed to the high-pressure arterial circulation.

As its name implies, thrombomodulin modulates the activity of thrombin from that of a procoagulant to an anticoagulant protease.⁴ When bound to thrombomodulin on the endothelial surface, thrombin is unable to generate fibrin or activate platelets but instead becomes a potent activator of protein C (see Figure). The activated form of protein C (APC) is an anticoagulant protease that selectively inactivates coagulation factors Va and VIIIa, providing an essential feedback mechanism to prevent excessive coagulation. Although activation of protein C in vivo is completely dependent on thrombomodulin, the efficiency of protein C activation is enhanced by another endothelial cofactor, the endothelial protein C receptor (EPCR).⁵ The clinical importance of the thrombomodulin/protein C anticoagulant pathway is underscored by the strong association between venous thromboembolism and resistance to APC caused by factor V Leiden.⁶

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