Kurzfassung

Activation of platelets is vital to the hemostatic process and a promising drug target to counteract thrombosis. Redox mechanisms significantly contribute to a pro-thrombotic state, because enhanced formation of reactive oxygen species (ROS) provokes an inflammatory milieu. This drives activation of endothelial cells and platelets, favors their interaction and facilities atherothrombosis. Our knowledge about proteins that mediate redox control particularly in platelets is limited. The NADPH...Activation of platelets is vital to the hemostatic process and a promising drug target to counteract thrombosis. Redox mechanisms significantly contribute to a pro-thrombotic state, because enhanced formation of reactive oxygen species (ROS) provokes an inflammatory milieu. This drives activation of endothelial cells and platelets, favors their interaction and facilities atherothrombosis. Our knowledge about proteins that mediate redox control particularly in platelets is limited. The NADPH oxidase NOX2 has been proposed as major pro-oxidative enzyme. In addition, our preliminary studies demonstrate an equally important role of the anti-oxidant protein paraoxonase 2 (PON2). This project addresses their specific functions in platelet activation and thrombosis. To this end, we plan to document NOX2/PON2 contributions to platelet redox homeostasis, calcium signaling, secretion and aggregation. Their impact on multicellular interactions, i.e. platelet adhesion to endothelial cells, will be studied in ex vivo flow chamber experiments and in in vivo thrombosis models. Pharmacologic NOX inhibitors will also be tested as strategy for normalization of redox control. Our research project integrates with other Center of Thrombosis (CTH) Groups / Platforms or University Medical Center (UMC) core institutes. We establish major scientific advancement due to the central function of redox control in cell activation and platelet-endothelial interactions in thrombosis.» weiterlesen» einklappen