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Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory

M Noutsias¹, B Seeberg, H P Schultheiss

¹Department of Cardiology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany. noutsias@zedat,fu-berlin.de

|April 27, 1999

Insights

Inflammatory endothelial activation is common in dilated cardiomyopathy (DCM) patients, with cell adhesion molecules (CAMs) correlating with inflammatory cardiomyopathy (InfCM) and intramyocardial infiltrates, suggesting diagnostic potential.

Area of Science:

Cardiovascular Pathology
Immunology
Molecular Biology

Background:

Dilated cardiomyopathy (DCM) is linked to inflammatory cardiomyopathy (InfCM), characterized by intramyocardial infiltration.
Cell adhesion molecules (CAMs) mediate the transendothelial migration of immunocompetent cells.

Purpose of the Study:

To investigate the expression patterns of various CAMs in endomyocardial biopsies from DCM patients.
To determine the correlation between CAM expression, inflammatory endothelial activation, and InfCM diagnosis.

Main Methods:

Immunohistochemistry was used to analyze CAM expression in 152 DCM patient biopsies and 14 control autopsy specimens.
CAMs evaluated included immunoglobulin superfamily members, selectins, and beta1/beta2-integrins.
Inflammatory endothelial activation and InfCM were assessed based on specific marker expression and cellular infiltration thresholds.

Main Results:

67% of DCM biopsies showed inflammatory endothelial activation, and 64% were positive for InfCM.
CAM expression correlated significantly with intramyocardial infiltrates.
Specific CAMs like vascular cell adhesion molecule-1 and selectins showed accentuated expression on single vascular endothelia.

Conclusions:

Inflammatory endothelial activation is a significant finding in a majority of DCM patients.
CAM evaluation in endomyocardial biopsies may hold diagnostic significance for InfCM.
CAM expression patterns provide insights into the inflammatory processes underlying DCM.

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Abstract

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 beta1- and beta2-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.

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