Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans

OBJECTIVE The expression of endothelial adhesion molecules and their functi onal significance in leukocyte adhesion to human myocardial blood vessels i n acute myocardial infarction (AMI) were studied. BACKGROUND Leukocyte extravasation, mediated by specific adhesion molecules , exacerbates tissue injury after restoration of blood supply to an ischemi c tissue. Experimental myocardial reperfusion injury can be alleviated with antibodies that block the function of adhesion molecules involved in leuko cyte emigration, but the relevant molecules remain poorly characterized in human METHODS Semiquantitative immunohistochemistry and in vitro adhesion assays were used to study the expression and granulocyte binding abilities of diff erent endothelial adhesion molecules in human AMI. Changes in the molecular nature of vascular adhesion protein-1 (VAP-1) were evaluated using immunob lotting. RESULTS Certain endothelial adhesion molecules (intercellular adhesion mole cule [ICAM-2], CD31 and CD73) were expressed in myocardial blood vessels ho mogeneously in normal and ischemic hearts, whereas others (E-selectin and p eripheral lymph node addressin) were completely absent from all specimens. The synthesis of ICAM-1 was locally, and that of P-selectin regionally, upr egulated in the infarcted hearts when compared with nonischemic controls. V ascular adhesion protein-1 showed ventricular preponderance in expression a nd alterations in posttranslational modifications during ischemia-reperfusi on. Importantly, P-selectin, ICAM-1 and VAP-1 mediated granulocyte binding to blood vessels in the ischemic human heart. CONCLUSION Human P-selectin, ICAM-1 and VAP-1 appear to be the most promisi ng targets when antiadhesive interventions preventing leukocyte-mediated ti ssue destruction after myocardial ischemia are planned. (J Am Cell Cardiol 2000;36:122-9) (C) 2000 by the American College of Cardiology.