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Neural cell adhesion molecule expression in dilated cardiomyopathy is associated with intramyocardial inflammation

Karsten Ostermann1, Heinz-Peter Schultheiss2, Michel Noutsias3

  • 1Department of Cardiology and Pneumonology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.

International Journal of Cardiology
|March 28, 2017
PubMed

Insights

Neural cell adhesion molecule (NCAM) is expressed in about half of adult dilated cardiomyopathy hearts, correlating with inflammation and cardiomyocyte enlargement. This suggests inflammatory pathways may induce NCAM in DCM.

Area of Science:

  • Cardiovascular pathology
  • Immunohistochemistry
  • Molecular biology

Background:

  • Chronic intramyocardial inflammation, known as inflammatory cardiomyopathy (DCMi), is implicated in dilated cardiomyopathy (DCM) pathogenesis.
  • Neural cell adhesion molecule (NCAM) plays a role in cardiac development but is typically downregulated in adult hearts.

Purpose of the Study:

  • To investigate Neural cell adhesion molecule (NCAM) expression in adult DCM hearts.
  • To assess the association between NCAM expression and DCMi parameters.
  • To examine the relationship between NCAM expression and cardiomyocyte hypertrophy (CMH).

Main Methods:

  • Endomyocardial biopsies (EMBs) from 85 DCM patients and 17 controls were immunostained for DCMi markers and NCAM.
  • Digital image analysis (DIA) quantified NCAM expression and inflammatory cell infiltrates.
  • Multivariate analysis examined associations between NCAM, inflammation markers, and cardiomyocyte size.

Main Results:

  • NCAM expression was found on cardiomyocytes in 54% of DCM patients, but not in controls.
  • NCAM expression (area fraction) was significantly higher in DCM hearts compared to controls (p=0.0001).
  • NCAM expression correlated significantly with inflammatory infiltrates (CD18+, CD11a/LFA-1+, CD11b/Mac-1+, TNFα+, CD3+) and endothelial cell adhesion molecules (ICAM-1, CD29).
  • Mean cardiomyocyte diameter (cardiomyocyte hypertrophy) strongly correlated with NCAM expression and inflammatory markers.

Conclusions:

  • NCAM expression occurs in approximately 50% of adult DCM hearts.
  • NCAM expression in DCM is associated with cardiomyocyte hypertrophy.
  • Inflammatory pathways may induce NCAM expression in the adult DCM heart.

Keywords:
Cell adhesion moleculesCytokinesDigital image analysisDilated cardiomyopathyEndomyocardial biopsiesHypertrophyImmunohistochemistryInflammationInflammatory cardiomyopathyNCAMNeural cell adhesion moleculeTNF

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