Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice.
The role of plasminogen (Plg) and alpha2-antiplasmin (alpha2-AP) in vascular thrombolysis in vivo was investigated in mice deficient in plasminogen (Plg-/-) or a2-AP (alpha2-AP-/-) or their wild type (PAI-1+/+, alpha2-AP+/+). A thrombus was induced in the murine carotid artery or the internal jugular vein by endothelial injury. Blood flow was continuously monitored for 90 min and for 6 h 30 min after the initiation of endothelial injury. The times to occlusion by the developing thrombus in the carotid artery and the jugular vein of wild type mice were 12+/-1.8 and 7.2+/-1.9 min, respectively. The arterial thrombus formation in alpha2-AP-/- mice was indistinguishable from the one in wild type mice, whereas the time to occlusion in Plg-/- was significantly shortened to 5.9+/-1.7 min. Vascular patency after spontaneous reperfusion was markedly improved in alpha2-AP-/- mice. On the contrary, arteriarpatency in Plg-/- mice was aggravated. In venous thrombus formation, the time to occlusion in alpha2-AP-/- mice was significantly prolonged (27.1+/-5.2 min), whereas in Plg-/- it was slightly shortened to 6.5+/-2.5 min. Vascular patency after spontaneous reperfusion was also improved in alpha2-AP-/- mice, but not in Plg-/- mice. Histological observations using SEM indicated that fibrin nets were firmly fixed on the injured area in Plg-/- mice, but not in alpha2-AP-/- mice. The tail bleeding time was not different in any type of mice. However, re-bleeding time using a template bleeding device was significantly prolonged in alpha2-AP-/- as compared with that of wild type mice. In conclusion, lack of plasminogen markedly reduces the antithrombotic activities in vivo, whereas alpha2-AP plays a more important role in the formation and removal of venous thrombus in mice. Consequently, the inhibition of alpha2-AP could be a useful tool for the therapy of venous thrombosis and the prevention of re-thrombus formation.
Matsuno
Hiroyuki
H
Department of Pharmacology, Gifu University School of Medicine, Japan. leuven@cc.gifu-u.ac.jp
Kozawa
Osamu
O
Okada
Kiyotaka
K
Ueshima
Shigeru
S
Matsuo
Osamu
O
Uematsu
Toshihiko
T
D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation / Q000502:physiology; D020212:Carotid Artery Injuries / Q000150:complications; D002341:Carotid Artery Thrombosis / Q000097:blood* / Q000209:etiology; D004730:Endothelium, Vascular / Q000293:injuries; D005341:Fibrinolysin / Q000096:biosynthesis / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology; D007601:Jugular Veins; D051379:Mice; D018345:Mice, Knockout; D010777:Photochemistry; D010958:Plasminogen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012008:Recurrence; D015424:Reperfusion; D012395:Rose Bengal / Q000528:radiation effects / Q000633:toxicity; D020246:Venous Thrombosis / Q000097:blood* / Q000209:etiology; D000979:alpha-2-Antiplasmin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000979:alpha-2-Antiplasmin; D012395:Rose Bengal; D010958:Plasminogen; D005341:Fibrinolysin