Antithrombin III-beta associates more readily than antithrombin III-alpha with uninjured and de-endothelialized aortic wall in vitro and in vivo.
The properties of two isoforms, alpha and beta, of rabbit antithrombin III (ATIII) were compared in the presence of undamaged or de-endothelialized rabbit aortic wall. Similar quantities of ATIII-alpha and ATIII-beta bound to and rapidly saturated the endothelium in vitro, but the rate of transendothelial passage of ATIII-beta exceeded that of ATIII-alpha by 22%. Furthermore, ATIII-beta was adsorbed approximately twice as rapidly as ATIII-alpha by the subendothelium of the de-endothelialized aorta. Binding of both isoforms was decreased (ATIII-beta more than ATIII-alpha) by pretreating the subendothelial surface with heparitinase. Also, subendothelium-bound ATIII-beta was desorbed more readily than bound ATIII-alpha by thrombin. In vivo, the rate of uptake of iodine-131-labeled ATIII-beta from the circulation by the aortic wall and the major organs was 30-50% faster than that of iodine-125-labeled ATIII-alpha. In contrast, the uptake of 131I-ATIII-beta by the de-endothelialized aorta in vivo was three times faster than that of 125I-ATIII-alpha. By these criteria, ATIII-beta is the more active of the two isoforms. We surmise that plasma and, consequently, vessel wall levels of ATIII-beta may be vital for controlling thrombogenic events caused by injury to the vascular wall.
Witmer
M R
MR
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Hatton
M W
MW
D000327:Adsorption; D000818:Animals; D000990:Antithrombin III / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011817:Rabbits; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology
D007457:Iodine Radioisotopes; D000990:Antithrombin III; D013917:Thrombin; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase