Ability of high-affinity heparin fractions with decreasing affinity for antithrombin III to activate ATIII isoforms.
Previous studies investigated the effect of heparin fractions on the rates of thrombin inhibition by naturally occurring antithrombin III (ATIII) isoforms differing in affinity for heparin. Heparin with low-affinity for ATIII increased the rate of thrombin inhibition by the higher affinity isoform about 10-fold more effectively than by the other isoform. This paper reports on the effect of a series of high-affinity heparin fractions with decreasing affinity for ATIII. As affinity decreased, the ability of the heparin fractions to increase the rate of the ATIII-thrombin reactions decreased, and these fractions slightly more effectively increased the rate of thrombin inhibition by the higher-affinity ATIII isoform. The effect of the heparin fractions on the ATIII-factor Xa reactions was also investigated. The activity of the fractions in this reaction also showed a dependence on ATIII-affinity. Studies on the competition of isoforms for immobilized heparin showed that the isoform with higher affinity for ATIII effectively competes with its congener for binding to heparin. The results indicate that heterogeneity in high-affinity heparin results in heterogeneity in affinity for ATIII that is significantly correlated with the ability of the heparin to potentiate ATIII-protease reactions. In spite of about equal activation of the ATIII isoforms by high-affinity heparin, the importance of the higher-affinity isoform is indicated by its ability to compete effectively for these heparin species.
Carlson
T H
TH
Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87110.
Kolman
M R
MR
Frees
A
A
Babcock
T
T
D000990:Antithrombin III / Q000378:metabolism*; D001667:Binding, Competitive; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism
D065427:Factor Xa Inhibitors; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin