At sites of vascular injury, platelets adhere, become activated and, together with fibrin generated by the coagulation cascade, form a stable plug which seals the wound. On the other hand, uncontrolled platelet activation in diseased vessels, such as found in patients with atherosclerosis, may lead to complete vessel occlusion (thrombosis), thrombus embolization, and thereby to life-threatening ischemia in heart, brain or other organs.
To better understand the processes underlying thrombotic diseases and to develop novel treatment options for with a good safety profile, we study the classical role of platelets in arterial thrombosis and hemostasis. Our work is focused on identifying platelet surface receptors and intracellular signaling pathways involved in thrombus formation by using transgenic mouse models, antibody targeting of surface receptors and various pharmacological approaches. Still a matter of investigation e.g. is the composition of thrombotic platelet aggregates and hemostatic plaques. In vitro assays are limited due to the inability to mimic the myriads of hemodynamic and spatiotemporal cellular and molecular interactions that occur during the generation and growth of thrombi in vivo. These limitations can be overcome by studying thrombus formation in the vascular system of a living organism.
In our laboratory, multiple murine in vivo models of arterial thrombosis have been established. We apply different stimuli to induce endothelial lesion, including chemically induced damage in small arterioles and mechanically induced endothelial denudation in large arteries. To monitor thrombus formation in vivo, we use intravital microscopy techniques together with fluorescent probes including fluorescently labeled antibodies and genetically encoded fluorescent indicators, thereby allowing the visualization of different aspects of thrombus formation in real-time. Alternatively, a doppler flow probe can be used to monitor blood flow and to determine vessel occlusion.
Although murine thrombosis models can only to a certain extent mimic the complex situation encountered in patients, studies of thrombus formation in mice provide an important step towards a better understanding of the molecular mechanisms underlying atherothrombosis in humans and thereby allow predictions for potential novel antithrombotic targets or therapies.