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Roles of Coagulation and Fibrinolysis in Angiotensin II ‐Enhanced Microvascular Thrombosis
Author(s) -
Senchenkova Elena Y.,
Russell Janice,
Esmon Charles T.,
Granger D. Neil
Publication year - 2014
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12120
Subject(s) - thrombus , fibrinolysis , antithrombin , coagulation , medicine , thrombosis , protein c , angiotensin ii , heparin , endocrinology , receptor
Objective Ang II ‐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 Ang II ‐mediated microvascular thrombosis. Methods Light/dye‐induced thrombus formation (the time of onset and flow cessation) was quantified in cremaster muscle arterioles of Ang II infused (two weeks) WT /Ang II mice, EPCR‐TgN, and mice deficient in PAI ‐1. WT /Ang II 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 Ang II ‐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 Ang II ‐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 Ang II and suggest that an impaired protein C pathway and increased PAI ‐1 do not make a significant contribution to this model of microvascular thrombosis.