Glycosaminoglycan Neutralization in Coagulation Control

Arterioscler Thromb Vasc Biol. 2018 Jun;38(6):1258-1270. doi: 10.1161/ATVBAHA.118.311102. Epub 2018 Apr 19.

Abstract

The glycosaminoglycans (GAGs) heparan sulfate, dermatan sulfate, and heparin are important anticoagulants that inhibit clot formation through interactions with antithrombin and heparin cofactor II. Unfractionated heparin, low-molecular-weight heparin, and heparin-derived drugs are often the main treatments used clinically to handle coagulatory disorders. A wide range of proteins have been reported to bind and neutralize these GAGs to promote clot formation. Such neutralizing proteins are involved in a variety of other physiological processes, including inflammation, transport, and signaling. It is clear that these interactions are important for the control of normal coagulation and influence the efficacy of heparin and heparin-based therapeutics. In addition to neutralization, the anticoagulant activities of GAGs may also be regulated through reduced synthesis or by degradation. In this review, we describe GAG neutralization, the proteins involved, and the molecular processes that contribute to the regulation of anticoagulant GAG activity.

Keywords: dermatan sulfate; glycosaminoglycan; heparan sulfate; heparin; thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Binding Sites
  • Blood Coagulation / drug effects*
  • Dermatan Sulfate / antagonists & inhibitors
  • Dermatan Sulfate / blood
  • Glycosaminoglycans / antagonists & inhibitors*
  • Glycosaminoglycans / blood
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Heparin Antagonists / adverse effects
  • Heparin Antagonists / therapeutic use*
  • Heparitin Sulfate / antagonists & inhibitors
  • Heparitin Sulfate / blood
  • Humans
  • Protein Binding

Substances

  • Anticoagulants
  • Glycosaminoglycans
  • Heparin Antagonists
  • Dermatan Sulfate
  • Heparin
  • Heparitin Sulfate