(Circulation. 1999;99:2124-2131.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Expression of Cell Adhesion Molecules in Dilated Cardiomyopathy
Evidence for Endothelial Activation in Inflammatory Cardiomyopathy
From the Department of Cardiology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany.
Correspondence to Michel Noutsias, Department of Cardiology, University Hospital Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. E-mail noutsias{at}zedat.fu-berlin.de
Background—Dilated cardiomyopathy (DCM) is pathogenically linked to inflammatory cardiomyopathy (InfCM), which is characterized by intramyocardial infiltration. The transendothelial migration of immunocompetent cells is mediated by cell adhesion molecules (CAMs).
Methods and Results—We investigated the expression pattern of CAMs (immunoglobulin superfamily, 32 selectins, and ß1- and ß2-integrins) in endomyocardial biopsies from DCM patients (n=152; left ventricular ejection fraction <40%) using immunohistochemistry. Whereas few specimens obtained at autopsy (controls; n=14) presented enhanced expression regarding single endothelial CAMs (human leukocyte antigen [HLA] class I, 7%; HLA-DR, 14%; CD29, 14%), none demonstrated concurrent abundance of >3 CAMs (inflammatory endothelial activation), nor did any control tissue prove positive for InfCM (>7.0 CD3+ lymphocytes per 1 mm2). In comparison, 64% (n=97) of the DCM biopsies were evaluated positive for InfCM and 67% (n=101) for inflammatory endothelial activation, respectively. Whereas expression of HLA class I, HLA-DR, intercellular cell adhesion molecule-1, and CD29 was distributed homogeneously within a patient's serial sections, immunoreactivity of vascular cell adhesion molecule-1, lymphocyte function antigen-3, and the selectins was accentuated on single vascular endothelia. Sixty-six percent of the DCM biopsies presented CD29 abundance also within the extracellular matrix and the sarcolemma. CD62P and CD62E were present in 16% and 40% of the DCM patients, respectively. Endothelial CAM representatives correlated with one another (P<0.05), except for CD62P with HLA. Endothelial CAM expression correlated with intramyocardial infiltrates phenotyped by the corresponding counterreceptors.
Conclusions—Inflammatory endothelial activation is present in 67% of DCM patients. Because CAM expression correlates with the immunohistological diagnosis of InfCM and counterreceptor-bearing intramyocardial infiltrates, evaluation of endothelial CAMs might be of diagnostic significance in InfCM.
Key Words: cardiomyopathy • diagnosis • cell adhesion molecules • endothelium • immune system • immunohistochemistry
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