title: Vitronectin receptor (alpha(v)beta3) mediates platelet adhesion to the luminal aspect of endothelial cells: implications for reperfusion in acute myocardial infarction.
abstract: BACKGROUND
  Platelet interaction with endothelium plays an important role in the pathophysiology of coronary microcirculation. We assessed the role of the vitronectin receptor (integrin alpha(v)beta3) in platelet/endothelium adhesion.
  
  
  RESULTS
  We investigated the effect on platelet/endothelium adhesion of plasma obtained from patients with acute myocardial infarction during reperfusion (before and 8, 24, 48, and 72 hours and 5 to 7 days after direct angioplasty) and with pretreatment with alpha-thrombin (2 U/mL) and recombinant human interleukin-1beta. Platelet/endothelium adhesion was significantly enhanced by approximately 20% after pretreatment of endothelium with patient plasma for 4 hours (P<.05) compared with endothelium treated with pooled control plasma. Plasma-induced platelet/endothelium adhesion was, in part, RGD peptide dependent. Pretreatment of endothelial cells with alpha-thrombin or recombinant human interleukin-1beta enhanced platelet/endothelium adhesion and surface expression of alpha(v)beta3 on the luminal aspect of endothelium (P<.05). The adhesion of platelets, isolated platelet microparticles, and Chinese hamster ovary cells bearing human recombinant alpha(IIb)beta3 (platelet glycoprotein IIb-IIIa) to activated endothelial cells was inhibited by antiadhesive peptides GRGDSP and c(RGDfV) and monoclonal antibodies 4F10, LM609, and 7E3.
  
  
  CONCLUSIONS
  The expression of vitronectin receptor exposed on the luminal aspect of activated endothelium is enhanced and mediates platelet/endothelium adhesion. Vitronectin receptor-mediated platelet attachment to activated endothelium during reperfusion may contribute to reperfusion injury and could be a target for antiadhesive therapy.
authors.affiliation: 1. Medizinische Klinik der Technischen Universität München, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
authors.forename: F J
authors.initials: FJ
authors.lastname: Neumann
authors.forename: T
authors.initials: T
authors.lastname: Dickfeld
authors.forename: A
authors.initials: A
authors.lastname: Reininger
authors.forename: H
authors.initials: H
authors.lastname: Adelsberger
authors.forename: A
authors.initials: A
authors.lastname: Gebhardt
authors.forename: A
authors.initials: A
authors.lastname: Schömig
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001798:Blood Proteins / Q000494:pharmacology; D016466:CHO Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000954:Antigens, Surface; D001798:Blood Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C057986:echistatin; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline