title: Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans.
abstract: OBJECTIVE
  The expression of endothelial adhesion molecules and their functional significance in leukocyte adhesion to human myocardial blood vessels in acute myocardial infarction (AMI) were studied.
  
  
  BACKGROUND
  Leukocyte extravasation, mediated by specific adhesion molecules, exacerbates tissue injury after restoration of blood supply to an ischemic tissue. Experimental myocardial reperfusion injury can be alleviated with antibodies that block the function of adhesion molecules involved in leukocyte emigration, but the relevant molecules remain poorly characterized in human AMI.
  
  
  METHODS
  Semiquantitative immunohistochemistry and in vitro adhesion assays were used to study the expression and granulocyte binding abilities of different endothelial adhesion molecules in human AMI. Changes in the molecular nature of vascular adhesion protein-1 (VAP-1) were evaluated using immunoblotting.
  
  
  RESULTS
  Certain endothelial adhesion molecules (intercellular adhesion molecule [ICAM-2], CD31 and CD73) were expressed in myocardial blood vessels homogeneously in normal and ischemic hearts, whereas others (E-selectin and peripheral lymph node addressin) were completely absent from all specimens. The synthesis of ICAM-1 was locally, and that of P-selectin regionally, upregulated in the infarcted hearts when compared with nonischemic controls. Vascular adhesion protein-1 showed ventricular preponderance in expression and alterations in posttranslational modifications during ischemia-reperfusion. Importantly, P-selectin, ICAM-1 and VAP-1 mediated granulocyte binding to blood vessels in the ischemic human heart.
  
  
  CONCLUSIONS
  Human P-selectin, ICAM-1 and VAP-1 appear to be the most promising targets when antiadhesive interventions preventing leukocyte-mediated tissue destruction after myocardial ischemia are planned.
authors.affiliation: National Public Health Institute and MediCity Research Laboratory, University of Turku, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Jaakkola
authors.forename: S
authors.initials: S
authors.lastname: Jalkanen
authors.forename: K
authors.initials: K
authors.lastname: Kaunismäki
authors.forename: E
authors.initials: E
authors.lastname: Vänttinen
authors.forename: P
authors.initials: P
authors.lastname: Saukko
authors.forename: K
authors.initials: K
authors.lastname: Alanen
authors.forename: M
authors.initials: M
authors.lastname: Kallajoki
authors.forename: L M
authors.initials: LM
authors.lastname: Voipio-Pulkki
authors.forename: M
authors.initials: M
authors.lastname: Salmi
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D019007:P-Selectin / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D015720:5'-Nucleotidase