title: Novel mechanistic concept of platelet inhibition.
abstract: BACKGROUND
  Activation of circulating platelets by exposed vessel wall collagen is a primary step in the pathogenesis of thrombotic diseases such as heart attack and stroke. Drugs that are capable of blocking platelet activation successfully reduce cardiovascular mortality and morbidity. However, despite intensive research efforts in antithrombotic drug discovery and development, uncontrolled hemorrhage still remains the most common side effect associated with antithrombotic drugs that are currently in use.
  
  
  OBJECTIVE
  The selective inhibition of glycoprotein VI (GPVI), the central platelet collagen receptor, and/or its signaling may inhibit thrombosis without affecting hemostatic plug formation. However, the mechanism of GPVI signaling is not known, hindering the further development of this promising antithrombotic strategy.
  
  
  METHODS
  This review focuses on an innovative mechanistic concept of platelet inhibition.
  
  
  CONCLUSIONS
  A novel model of GPVI signaling, the signaling chain homooligomerization (SCHOOL) model, has revealed new therapeutic targets for GPVI inhibition, resulting in the development of novel antithrombotic pharmacological approaches and the invention of new platelet inhibitors.
authors.affiliation: University of Massachusetts Medical School, Department of Pathology, 55 Lake Avenue North, Worcester, MA 01655, USA. Alexander.Sigalov@umassmed.edu
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Sigalov
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D006801:Humans; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010980:Platelet Membrane Glycoproteins