Targeting GPVI: impact of modulating platelet-collagen interactions on receptor signaling and thrombus formation

Platelets are blood cells that prevent the loss of extensive blood volumes, but also contribute to arterial thrombosis. After a vessel is injured, platelets become activated by the exposed collagen and aggregate together, forming a thrombus. Whilst this is a crucial process in hemostasis, platelets also become activated due to rupture of an atherosclerotic plaque in atherothrombosis. Herein, leading to for example, myocardial infarction, stroke or transient ischemic attacks, mediated by collagen that is present in the atherosclerotic plaque. These events are still leading causes of death world-wide, and patients are usually prescribed anti-platelet drugs to prevent a second thrombosis. Currently used drugs are effective in preventing thrombosis, but they are prone to causing unwanted bleeding events in some of the patients. Therefore, other treatment options are currently investigated. A promising approach is to prevent platelet-collagen interactions via inhibition of the collagen receptor, glycoprotein VI (GPVI). In this thesis, we compared the various approaches used to interfere in the GPVI-dependent interaction of platelets with collagens. This was done by a whole blood flow chamber set up with collagen coatings, assessing the effects on thrombus formation.