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Interactions of hemostatic proteins with the vasculature: go with the flow?

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Maartje van den Biggelaar



Hemostasis is the biological process that prevents and stops bleeding. It is achieved by a delicate triadic interplay between the vessel wall, blood platelets and coagulation factors. It has become increasingly clear that blood flow is an integral part of hemostasis, and that interactions of circulating cells and proteins with the vasculature are regulated by blood flow. Yet, hemodynamics is completely overlooked in most studies on hemostatic protein interactions with the vasculature.
Via a variety of mechanosensors on their cell surface, endothelial cells sense flow and transmit mechanical signals through signaling pathways that affect endothelial development, phenotype and function. Therefore, it is critical to understand how the vasculature responds to flow and how mechanosensory protein-receptor interactions are regulated at the molecular level. To understand cellular responses as a result of hemostatic interactions and to reveal the mechanisms and complexity of coagulation-induced signaling, systems biological approaches are required to simultaneously monitor and integrate cross-talk among multiple signaling cascades.

In this project we have developed and applied mass spectrometry-based approaches to study the response of the vasculature to inflammatory signals, hemodynamics, and key players of primary hemostasis (platelets, VWF) and secondary hemostasis (coagulation factors). Using multi-omic approaches we revealed novel aspects of these individual processes as well as aspects of the interplay between blood flow, hemostasis and inflammation

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