Elena Y Senchenkova1, Janice Russell, Charles T Esmon, D Neil Granger. 1. Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana, USA; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Saint-Petersburg, Russia.
Abstract
OBJECTIVE: AngII-induced HTN is associated with accelerated thrombus development in arterioles. This study assessed the contributions of different components of the coagulation cascade and fibrinolysis to AngII-mediated microvascular thrombosis. METHODS: Light/dye-induced thrombus formation (the time of onset and flow cessation) was quantified in cremaster muscle arterioles of AngII infused (two weeks) WT/AngII mice, EPCR-TgN, and mice deficient in PAI-1. WT/AngII mice were also treated with either tissue factor antibody, antithrombin III, heparin, hirudin, or murine APC. RESULTS: TF immunoblockade or hirudin treatment did not prevent the AngII-induced acceleration of thrombosis. While antithrombin III treatment prevented the acceleration in both thrombus onset and flow cessation, heparin only improved the time for blood flow cessation. Neither WT mice treated with murine APC nor EPCR-TgN were protected against AngII-induced thrombus development. A similar lack of protection was noted in PAI-1deficient mice. CONCLUSION: These findings implicate a role for thrombin generation pathway in the accelerated thrombosis induced by AngII and suggest that an impaired protein C pathway and increased PAI-1 do not make a significant contribution to this model of microvascular thrombosis.
OBJECTIVE:AngII-induced HTN is associated with accelerated thrombus development in arterioles. This study assessed the contributions of different components of the coagulation cascade and fibrinolysis to AngII-mediated microvascular thrombosis. METHODS: Light/dye-induced thrombus formation (the time of onset and flow cessation) was quantified in cremaster muscle arterioles of AngII infused (two weeks) WT/AngIImice, EPCR-TgN, and mice deficient in PAI-1. WT/AngIImice were also treated with either tissue factor antibody, antithrombin III, heparin, hirudin, or murineAPC. RESULTS:TF immunoblockade or hirudin treatment did not prevent the AngII-induced acceleration of thrombosis. While antithrombin III treatment prevented the acceleration in both thrombus onset and flow cessation, heparin only improved the time for blood flow cessation. Neither WT mice treated with murineAPC nor EPCR-TgN were protected against AngII-induced thrombus development. A similar lack of protection was noted in PAI-1deficient mice. CONCLUSION: These findings implicate a role for thrombin generation pathway in the accelerated thrombosis induced by AngII and suggest that an impaired protein C pathway and increased PAI-1 do not make a significant contribution to this model of microvascular thrombosis.
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