Anticoagulant heparan sulfate to not clot--or not?

摘要: Vascular endothelial cells (ECs) produce anticoagulant heparan sulfate (HSAT+)-a small subpopulation of (HS) containing a specific pentasaccharide motif with high affinity for plasma antithrombin (AT). This is responsible the action therapeutic heparin, which dramatically catalyzes AT neutralization coagulation proteases. Consequently, HSAT+ has been designated as "anticoagulant HS," and long thought to convey antithrombotic properties blood vessel wall. The Hs3st1 gene encodes HS 3-O-sulfotransferase-1, whose rate limiting regulates EC production HSAT+. To elucidate biologic role HSAT+, we generated Hs3st1-/- knock-out mice that have undetectable Despite held historic expectations, hemostasis was unaffected in mice. In light this surprising finding, herein evaluate historic, biochemical, kinetic, physiologic, molecular genetic studies AT, We find hemostatic cannot presently be excluded; however, may well not essential AT's function. Specifically, absence glycosaminoglycans, physiologic levels can neutralize proteases at sufficiently throughput account most Moreover, wall surface, glycosaminoglycans distinct from predominant catalysts activity. then explore possibility less known function anti-inflammatory exhibit strong proinflammatory phenotype unresponsive conclude mediate