Roles of Coagulation and fibrinolysis in angiotensin II-enhanced 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/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.


CONCLUSIONS
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.
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.
Elena Y
EY
Senchenkova
Janice
J
Russell
Charles T
CT
Esmon
D Neil
DN
Granger
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D006490:Hemostatics / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D011486:Protein C / Q000235:genetics / Q000378:metabolism; D058258:Serpin E2 / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000494:pharmacology; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000991:Antithrombins; D006490:Hemostatics; D011486:Protein C; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000990:Antithrombin III; D013925:Thromboplastin; D013917:Thrombin
angiotensin II; anticoagulants; coagulation; fibrinolysis; thrombosis