Breakthrough discoveries from shear flow assays for Platelet biology and vascular studies

Dr. Pula group discovered agonist specificity of the activation of NADPH oxidases during platelet activation, with NOX1 prominently activated by collagen, while thrombin and other agonists activate both NOX1 and NOX2. The inhibition of NOX1 has strong antiplatelet effects in vitro. Collagen-dependent thrombus formation under flow is abolished by NOX1 inhibition in human platelets or genetic deletion in mouse platelets. Importantly, although thrombosis tested in vivo in carotid occlusion and pulmonary embolism assays is severely impaired by NOX1 inhibition, haemostasis remains unaffected. This suggests the possibility to design NOX1-specific drugs to be used as antithrombotics with no bleeding side effects. This work suggests how the modelling of thrombus formation by flow assays in vitro may find important applications in vascular biology and drug discovery

Dr. Giordano Pula, PhD
Group Leader for Haemostasis and Thrombosis
University Medical Center Eppendorf, University of Hamburg

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