Heparins designed to specifically inhibit platelet interactions with von Willebrand factor

Circulation
M SobelR B Harris

Abstract

Platelet interactions with the injured vessel wall may contribute significantly to the early and late failures of many cardiovascular interventions; the adhesive protein von Willebrand factor (vWF) is thought to play an important role. Previously, we demonstrated that heparin interfered with platelet/vWF hemostatic mechanisms by binding to vWF within the proteins's domain responsible for binding the platelet vWF receptor, glycoprotein Ib. The purpose of the present study was to develop and refine heparins with greater potency to inhibit platelet/vWF interactions. Immobilized synthetic peptides based on a known heparin-binding domain of vWF were used to yield novel fractions of standard heparin that demonstrated a sevenfold increase in their ability to inhibit vWF-dependent platelet agglutination and vWF/platelet binding. The high vWF affinity heparin showed enhanced anti-factor Xa activity but comparable activated partial thromboplastin time activity. Chemical modification of a standard heparin by periodate oxidation and borohydride reduction enhanced its ability to inhibit platelet/vWF interactions by threefold, while eliminating more than 90% of its activated partial thromboplastin time and anti-factor Xa activity. Affinity c...Continue Reading

References

Jun 2, 1992·Biochemistry·D S FerranR B Harris
Apr 1, 1991·The Journal of Clinical Investigation·Y IkedaI Itagaki
May 1, 1991·The Journal of Clinical Investigation·M SobelD Marques
Jan 1, 1985·Advances in Experimental Medicine and Biology·R M Hardisty
Jan 1, 1986·Annual Review of Medicine·R Moroose, L W Hoyer
Aug 1, 1973·Analytical Biochemistry·N Blumenkrantz, G Asboe-Hansen
Mar 1, 1983·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·B AdelmanR I Handin
Apr 1, 1994·Protein Science : a Publication of the Protein Society·R Tyler-CrossR B Harris
Apr 7, 1994·The New England Journal of Medicine·L A Harker

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Citations

Aug 10, 1999·Critical Reviews in Oncology/hematology·L L Horstman, Y S Ahn
Oct 1, 2013·Expert Opinion on Therapeutic Targets·Silvia Montoro-GarcíaGregory Y H Lip
Jun 3, 1999·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·C A HerzogC D Dick
Dec 13, 2005·Biochemical and Biophysical Research Communications·Tatsuya AdachiTomoki Naoe
Mar 10, 2001·Journal of Vascular Surgery·M SobelY Suda
Jun 7, 2016·International Journal of Cardiology·Giuseppe Cassinelli, Annamaria Naggi

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