title: Targeting glycoprotein VI and the immunoreceptor tyrosine-based activation motif signaling pathway.
abstract: Coronary artery thrombosis and ischemic stroke are often initiated by the disruption of an atherosclerotic plaque and consequent intravascular platelet activation. Thus, antiplatelet drugs are central in the treatment and prevention of the initial, and subsequent, vascular events. However, novel pharmacological targets for platelet inhibition remain an important goal of cardiovascular research because of the negative effect of existing antiplatelet drugs on primary hemostasis. One promising target is the platelet collagen receptor glycoprotein VI. Blockade or antibody-mediated depletion of this receptor in circulating platelets is beneficial in experimental models of thrombosis and thrombo-inflammatory diseases, such as stroke, without impairing hemostasis. In this review, we summarize the importance of glycoprotein VI and (hem)immunoreceptor tyrosine-based activation motif signaling in hemostasis, thrombosis, and thrombo-inflammatory processes and discuss the targeting strategies currently under development for inhibiting glycoprotein VI and its signaling.
authors.affiliation: From the Department of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Stegner
authors.affiliation: From the Department of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Haining
authors.affiliation: From the Department of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany. bernhard.nieswandt@virchow.uni-wuerzburg.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D006470:Hemorrhage / Q000139:chemically induced; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D061626:Immunoreceptor Tyrosine-Based Inhibition Motif; D058990:Molecular Targeted Therapy; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy
chemical_list: D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI
keywords: antiplatelet agents; immunoreceptor tyrosine-based activation motif; platelet inhibitors