Heparin cofactor II modulates the response to vascular injury.
Heparin cofactor II (HCII) has several biochemical properties that distinguish it from other serpins: (1) it specifically inhibits thrombin; (2) the mechanism of inhibition involves binding of an acidic domain in HCII to thrombin exosite I; and (3) the rate of inhibition increases dramatically in the presence of dermatan sulfate molecules having specific structures. Human studies suggest that high plasma HCII levels are protective against in-stent restenosis and atherosclerosis. Studies with HCII knockout mice directly support the hypothesis that HCII interacts with dermatan sulfate in the arterial wall after endothelial injury and thereby exerts an antithrombotic effect. In addition, HCII deficiency appears to promote neointima formation and atherogenesis in mice. These results suggest that HCII plays a unique and important role in vascular homeostasis.
Tollefsen
Douglas M
DM
Division of Hematology, Campus Box 8125, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110, USA. tollefsen@im.wustl.edu
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D023903:Coronary Restenosis / Q000503:physiopathology / Q000517:prevention & control; D003871:Dermatan Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D015844:Heparin Cofactor II / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D013927:Thrombosis / Q000503:physiopathology / Q000517:prevention & control*; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism
D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D013917:Thrombin