Vascular localization of the heparin-binding serpins antithrombin, heparin cofactor II, and protein C inhibitor

Heparin is one of the most widely used drugs in the world, acting as an anticoagulant by stimulating the reaction between heparin-binding serpins and the serine proteases of the coagulation cascade. To determine whether the heparin-binding serpins antithrombin (AT), heparin cofactor II (HCII), and protein C inhibitor (PCI) were bound to glycosaminoglycans on the endothelial wall, a bolus of heparin (100 U/kg body weight) was injected into human volunteers, and serpin concentrations and activities were measured in both pre- and postheparin plasma. No increase in circulating concentrations of AT, HCII, or PCI were observed in postheparin plasma. Similarly, AT and HCII activities did not increase in postheparin plasma. In contrast, the concentration of another heparin-binding protein, lactoferrin (LF), increased six-fold after heparin injection. Immunohistochemistry of human artery was performed using polyclonal antisera to AT, HCII, PCI, LF, and tissue factor pathway inhibitor (TFPI), another heparin-binding protein released by heparin injection. AT, HCII, and PCI were present in the intima, whereas LF, TFPI, and traces of AT were found on the surface of the vessel wall. The distribution of the proteins in the vessel wall supports the results of the heparin-injection studies and may give valuable clues to the role of each protein in vascular homeostasis. © 1996 Lippincott-Raven Publishers.

Duke Scholars

Author Maureane Hoffman Pathology