title: Platelet adhesion via glycoprotein IIb integrin is critical for atheroprogression and focal cerebral ischemia: an in vivo study in mice lacking glycoprotein IIb.
abstract: BACKGROUND
  The platelet glycoprotein (GP) IIb/IIIa integrin binds to fibrinogen and thereby mediates platelet aggregation. Here, we addressed the role of GP IIb for platelet adhesion and determined the relevance of platelet GP IIb for the processes of atherosclerosis and cerebral ischemia-reperfusion (I/R) injury.
  
  
  RESULTS
  GP IIb(-/-) mice were generated and bred with ApoE(-/-) animals to create GP IIb(-/-)ApoE(-/-) mice. Platelet adhesion to the mechanically injured or atherosclerotic vessel wall was monitored by in vivo video fluorescence microscopy. In the presence of GP IIb, vascular injury and early atherosclerosis induced platelet adhesion in the carotid artery (CA). In contrast, platelet adhesion was significantly reduced in the absence of GP IIb integrin (P<0.05). To address the contribution of platelet GP IIb to atheroprogression, we determined atherosclerotic lesion formation in the CA and aortic arch (AA) of GP IIb(+/+)ApoE(-/-) or GP IIb(-/-)ApoE(-/-) mice. Interestingly, the absence of GP IIb attenuated lesion formation in CA and AA, indicating that platelets, via GP IIb, contribute substantially to atherosclerosis. Next, we assessed the implication of GP IIb for cerebral I/R injury. We observed that after occlusion of the middle cerebral artery, the cerebral infarct size was drastically reduced in mice lacking GP IIb compared with wild-types.
  
  
  CONCLUSIONS
  These findings show for the first time in vivo that GP IIb not only mediates platelet aggregation but also triggers platelet adhesion to exposed extracellular matrices and dysfunctional endothelial cells. In a process strictly involving GP IIb, platelets, which are among the first blood cells to arrive at the scene of endothelial dysfunction, contribute essentially to atherosclerosis and cerebral I/R injury.
authors.affiliation: Deutsches Herzzentrum and 1. Medizinische Klinik, Technische Universität München, Lazarettstrasse 36, D-80636 Munich, Germany. massberg@dhm.mhn.de
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.forename: Katrin
authors.initials: K
authors.lastname: Schürzinger
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.forename: Ildiko
authors.initials: I
authors.lastname: Konrad
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kennerknecht
authors.forename: Martina
authors.initials: M
authors.lastname: Rudelius
authors.forename: Susanne
authors.initials: S
authors.lastname: Sauer
authors.forename: Siegmund
authors.initials: S
authors.lastname: Braun
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Nikla R
authors.initials: NR
authors.lastname: Emambokus
authors.forename: Jon
authors.initials: J
authors.lastname: Frampton
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood* / Q000235:genetics; D002450:Cell Communication / Q000502:physiology; D002544:Cerebral Infarction / Q000097:blood / Q000235:genetics; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D002537:Intracranial Arteriosclerosis / Q000097:blood* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010973:Platelet Adhesiveness / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics* / Q000378:metabolism*; D020521:Stroke / Q000097:blood / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D040201:Platelet Membrane Glycoprotein IIb