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CLINICAL STUDIES: MYOCARDIAL INFARCTION

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

Kimmo Jaakkola, MD^* , Sirpa Jalkanen, MD^*, Katja Kaunismäki, MD^*, Esko Vänttinen, MD, Pekka Saukko, MD, Kalle Alanen, MD^||, Markku Kallajoki, MD^||, Liisa-Maria Voipio-Pulkki, MD and Marko Salmi, MD^*

^* National Public Health Institute and MediCity Research Laboratory, University of Turku, Turku, Finland
Department of Medicine, University of Turku, Turku, Finland
Department of Surgery, University of Turku, Turku, Finland
Department of Forensic Medicine, University of Turku, Turku, Finland
^|| Department of Pathology, University of Turku, Turku, Finland

Manuscript received August 20, 1999; revised manuscript received January 18, 2000, accepted March 24, 2000.

Reprint requests and correspondence: Dr. Marko Salmi, MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520, Turku, Finland
marko.salmi{at}utu.fi

OBJECTIVES

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.

Abbreviations and Acronyms   AMI = acute myocardial infarction   EAM = endothelial adhesion molecule   ICAM = intercellular adhesion molecule   mAb = monoclonal antibody   PNAd = peripheral lymph node addressin   VAP-1 = vascular adhesion protein-1   VCAM-1 = vascular cell adhesion molecule-1

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