Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice.

Abstract

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.

• Authors: Hiroyuki Matsuno, Osamu Kozawa, Kiyotaka Okada, Shigeru Ueshima, Osamu Matsuo, Toshihiko Uematsu
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 87 Issue 1 Pg. 98-104 (Jan 2002) ISSN: 0340-6245 [Print] Germany
• PMID: 11848464 (Publication Type: Journal Article)

Chemical References

• alpha-2-Antiplasmin
• Rose Bengal
• Plasminogen
• Fibrinolysin

Topics

• Animals
• Bleeding Time
• Blood Coagulation (physiology)
• Carotid Artery Injuries (complications)
• Carotid Artery Thrombosis (blood, etiology)
• Endothelium, Vascular (injuries)
• Fibrinolysin (biosynthesis, physiology)
• Fibrinolysis (physiology)
• Jugular Veins
• Mice
• Mice, Knockout
• Photochemistry
• Plasminogen (deficiency, genetics, physiology)
• Recurrence
• Reperfusion
• Rose Bengal (radiation effects, toxicity)
• Venous Thrombosis (blood, etiology)
• alpha-2-Antiplasmin (deficiency, genetics, physiology)