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- W2103600164 abstract "Background: Multicellular interactions of platelets, coagulation factors, leukocytes and the vessel wall play pivotal roles in activating coagulation and precipitating arterial and venous thrombosis. High levels of angiotensin II (ATII) cause arterial hypertension by a complex inflammatory pathway requiring inflammatory leukocyte recruitment and reactive oxygen species (ROS) production within the vessel wall coupled to vascular dysfunction. How platelets, coagulation factors, leukocytes and the vessel wall cooperate to promote vascular inflammation is unclear. Methods and results: Here we delineate a novel non-thrombotic, FXI-dependent, pro-inflammatory coagulation pathway that substantially regulates vascular tone and endothelial function. We can demonstrate that pharmacological inhibition of the synthesis of FXI by an antisense-oligonucleotide (ASO) attenuates ATII-induced vascular dysfunction in acetylcholine-induced vascular relaxation. ATII-induced arterial hypertension, vascular inflammation and leukocyte infiltration are equally diminished by FXI ASO treatment. In addition, vascular ROS formation and fibrotic remodeling is blocked by FXI ASO treatment in ATII-infused mice. Accordingly, intravital microscopy video imaging (IVM) shows that ATII-induced leukocyte rolling as well as adhesion in the carotid artery is reduced by inhibition of the synthesis of FXI, whereas acute infusion of recombinant FXI is not able to restore ATII-driven leukocyte adhesion. Hence FXI is required continuously for the ATII-induced vascular pathology. We show that this pathway does not depend on FXII-dependent activation and that FXII-deficiency does not prevent from ATII-induced vascular dysfunction and inflammation. Conclusion: Our results provide novel insight into coagulation-inflammation circuits and point to broader utility of specific FXI-targeted anticoagulants beyond indications as antithrombitic agents in cardiovascular diseases." @default.
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- W2103600164 date "2015-05-01" @default.
- W2103600164 modified "2023-10-04" @default.
- W2103600164 title "Abstract 32: Coagulation Factor XI and Thrombin Mediate Angiotensin II-induced Vascular Dysfunction" @default.
- W2103600164 doi "https://doi.org/10.1161/atvb.35.suppl_1.32" @default.
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