Re-visiting the structure of heparin

Oversulfated heparins with low anticoagulant activity are strong and fast inhibitors of hepcidin expression in vitro and in vivo

“…acid (either D-glucuronic acid (GlcA) or L-iduronic acid (IdoA)) and D-glucosamine (either D-glucosamine N-acetylate (GlcNAc) or Dglucosamine N-sulfate (GlcNSO 3 )) and bear O-sulfate substituents in various positions [16], preferentially in position 2 of IdoA and in position 6 of GlcNSO 3 . The anticoagulant activity is mainly due to the high affinity binding to antithrombin (AT) through a specific and rare pentasaccharide sequence that has a central GlcNSO 3 sulfated at 3-O, flanked by an unsulfated GlcA and by a 2-O sulfated iduronic acid [17].…”

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: Insights into the physiological role of endogenous heparin

“…Whilst much is now known about the nature of commercially prepared pharmaceutical heparin, both in its unfractionated and low-molecular weight forms, with respect to structure, biological activity and clinical effects (2)(3)(4), the physiological role of endogenous heparin is considerably less well understood. It has long been known, however, that heparin possesses additional effects that are both separate to, and separable from, its well-characterized effects on blood coagulation, many of which involve modulation of aspects of immune or inflammatory cell function (5,6).…”

Old and new applications of non-anticoagulant heparin

“…The early reports of the beneficial effects of heparin in inflammation were attributed to the heparin binding and inhibition of chemokines, complement, growth and angiogenic factors, as reviewed recently [1,5,6,7]. Heparin can also bind to adhesion mediators expressed during inflammation, such as selectins, integrins and their receptors [8,9].…”

“…Heparin and LMWHs are widely used for the prevention and treatment of thrombotic events by inhibiting antithrombin III (AT) and factor Xa through a specific oligosaccharide binding sequence (ATBR) present in only one third of unfractionated heparin chains as has been well-documented in two recent reviews [1,2]. Heparin, the most negatively charged biopolymer has an average of four negative charges for each disaccharide unit, can interact with a wide range of proteins, with interactions that exhibit a range of specificities [3] and induce several associated biological activities.…”