Interaction of antithrombin III with bovine aortic segments. Role of heparin in binding and enhanced anticoagulant activity
Bovine antithrombin III (AT III) interaction with the luminal surface of bovine aortic segments with a continuous layer of endothelium was examined. Incubation of /sup 125/I-AT III with vessel segments, previously washed free of endogenous AT III, demonstrated specific, time-dependent binding to the protease inhibitor to the endothelium. Half-maximal binding was observed at an added AT III concentration of 14 nM. Binding of /sup 125/I-AT III to the vessel wall was reversible (50% dissociated in 4 min), and addition of either heparin or Factor Xa accelerated displacement of /sup 125/I-AT III from the vessel segment. Dissociation of /sup 125/I-AT III from the vessel segment in the presence of factor Xa coincided with the formation of a Factor Xa-/sup 125/I-AT III complex. Inactivation of Factor IXa and Factor Xa by AT III was facilitated in the presence of vessel segments. Pretreatment of vessel segments with highly purified Flavobacterium heparinase precluded the vessel-dependent augmentation of AT III anticoagulant activity as well as specific binding of /sup 125/I-AT III to the vessel endothelium. In contrast, pretreatment of the vessel segments with chrondroitinases (ABC or AC) had no detectable effect on /sup 125/I-AT III binding or on AT III anticoagulant activity. AT III binding to vessel segments was competitively inhibited by increasing concentration of platelet factor 4. Binding of the protease inhibitor to vessel segments was inhibited by chemical modification of AT III lysyl or tryptophan residues. These AT III derivatives retained progressive inhibitory activity. These data suggest that heparin-like molecules are present on the aortic vessel wall and mediate binding of AT III to the vessel surface, as well as enhancing the anticoagulant activity of AT III at these sites.
- Research Organization:
- Columbia Univ. Coll. of Physicians and Surgeons, New York
- OSTI ID:
- 5836699
- Journal Information:
- J. Clin. Invest.; (United States), Vol. 75:1
- Country of Publication:
- United States
- Language:
- English
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550201* - Biochemistry- Tracer Techniques