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• W2103171036 abstract "Objective— We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. Methods and Results— Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta ( P <0.01) and lung ( P <0.001). Activation of endogenous protein C following infusion of thrombin was decreased by 90% in knock-in mice compared with wild-type mice ( P <0.05). Carotid artery thrombosis induced by photochemical injury occurred more rapidly in knock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; P <0.05). No differences in serum cytokine levels were detected between knock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E–deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. Conclusion— Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo." @default.
• W2103171036 created "2016-06-24" @default.
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• W2103171036 date "2011-11-01" @default.
• W2103171036 modified "2023-10-14" @default.
• W2103171036 title "Human Thrombomodulin Knock-In Mice Reveal Differential Effects of Human Thrombomodulin on Thrombosis and Atherosclerosis" @default.
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• W2103171036 doi "https://doi.org/10.1161/atvbaha.111.236828" @default.
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