Deendothelialization in vivo initiates a thrombogenic reaction at the rabbit aorta surface. Correlation of uptake of fibrinogen and antithrombin III with thrombin generation by the exposed subendothelium.
Purified radiolabeled fibrinogen and antithrombin III (ATIII) were injected intravenously into rabbits before a deendothelializing injury to the aorta, and allowed to circulate for 0.1 to 6 hours before exsanguination, excision of the aorta, and quantification of each protein/unit area of subendothelium (intima-media). Uptake of fibrinogen was rapid (saturation 10 minutes after injury was approximately 13.0 pmol/cm2) compared with that of ATIII (45 to 60 minutes; 3.5 to 4.3 pmol/cm2). Both proteins associated primarily (greater than 90%) with the subendothelium rather than the platelet monolayer. The avidity of the deendothelialized vessel of these proteins was measured after a 20-minute circulation time at various intervals after injury. Whereas turnover of fibrinogen was fairly constant (approximately 100% per hour), that of ATIII was maximal (approximately 200% per hour) at 1 hour, decreasing to approximately 105% per hour at 5 hours after injury. The profile of ATIII turnover mirrored that of thrombin released in vitro from the deendothelialized aorta up to 10 days after injury, whereas the uninjured aorta and the aorta deendothelialized ex vivo adsorbed fibrinogen poorly and released negligible thrombin. Pretreatment of the aorta, deendothelialized ex vivo with thrombin in vitro increased fibrinogen uptake significantly. It is possible that, after deendothelialization in vivo, fibrinogen adsorption is determined largely by thrombin generation at the vessel wall. ATIII binding is limited by the availability of binding sites in the subendothelium, although the rate of thrombin generation influences ATIII turnover.
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
M W
MW
Hatton
S L
SL
Moar
M
M
Richardson
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D013917:Thrombin / Q000096:biosynthesis*
D000990:Antithrombin III; D005340:Fibrinogen; D013917:Thrombin