Vascular dermatan sulfate and heparin cofactor II.

Heparin cofactor II (HCII) is a plasma protease inhibitor of the serpin family that inactivates thrombin by forming a covalent 1:1 complex. The rate of complex formation increases more than 1000-fold in the presence of dermatan sulfate (DS). Endothelial injury allows circulating HCII to enter the vessel wall, where it binds to DS and presumably becomes activated. Mice that lack HCII develop carotid artery thrombosis more rapidly than wild-type mice after oxidative damage to the endothelium. These mice also have increased arterial neointima formation following mechanical injury and develop more extensive atherosclerotic lesions when made hypercholesterolemic. Similarly, low plasma HCII levels appear to be a risk factor for atherosclerosis and in-stent restenosis in human subjects. These observations suggest that a major function of the HCII-DS system is to regulate the physiologic response to arterial injury.