title: Binding of antithrombin to immobilized heparin under varying flow conditions.
abstract: Rheologic factors are likely to influence the balance between thrombotic and antithrombotic forces at the level of the vascular wall. In this study, the effects of flow-velocity/wall shear stress on the interaction of antithrombin (AT) with surface-immobilized heparin were investigated. The binding of AT to low-affinity and high-affinity heparin could be discriminated by measurements at physiological of elevated ionic strength. Under low shear stress conditions, substantial binding of AT to both high- and low-affinity heparin was observed, in relative quantities largely reflecting the proportion of these polysaccharide populations on the surface. With increasing shear stress, the binding to high-affinity sites was relatively constant, while total low-affinity binding decreased. Furthermore, under the highest shear stress (greater than 1,000 N/m2), the binding of AT to low-affinity heparin completely disappeared while binding to the high-affinity fraction persisted. These results were related to values obtained in a mathematical model, describing the theoretical maximum transport of AT from the liquid phase to the surface under the conditions used in the experimental system.
authors.affiliation: Department of Experimental Surgery, Karolinska Institute, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Pasche
authors.forename: G
authors.initials: G
authors.lastname: Elgue
authors.forename: P
authors.initials: P
authors.lastname: Olsson
authors.forename: J
authors.initials: J
authors.lastname: Riesenfeld
authors.forename: A
authors.initials: A
authors.lastname: Rasmuson
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000378:metabolism*; D001665:Binding Sites; D001783:Blood Flow Velocity; D006493:Heparin / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D012212:Rheology; D013314:Stress, Mechanical; D013499:Surface Properties
chemical_list: D000991:Antithrombins; D006493:Heparin