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

Abstract

Chronic intramyocardial inflammation (inflammatory cardiomyopathy/DCMi) is linked to the pathogenesis of dilated cardiomyopathy (DCM). Neural cell adhesion molecule (NCAM) is involved in orchestrating cardiac muscle morphogenesis, but is down-regulated after embryogenesis. We investigated NCAM expression in adult DCM hearts, its possible association with DCMi-parameters, and with cardiomyocyte hypertrophy (CMH). Endomyocardial biopsies (EMBs) from DCM patients (n=85; n=37 females; age: 48±19years; LVEF <40%) and controls from non-cardiac deaths were immunostained for DCMi markers and for NCAM expression, and quantified by digital image analysis (DIA). NCAM expression on the intercalated discs and the sarcolemma was confirmed in n=46 (54%) of the DCM-EMBs. In the 17 controls, NCAM expression was confined to scattered intramyocardial nerves, but was absent on cardiomyocytes. DIA-quantified area fraction (AF) of NCAM was significantly (p=0.0001) higher in the DCM hearts (0.0044±0.017) compared with the controls (0.0006±0.0004). Multivariate analysis of DIA-quantified NCAM-AF revealed significant associations with infiltrates (CD18+, CD11a/LFA-1+, CD11b/Mac-1+, TNFα+, CD3+) and with endothelial cell adhesion molecules (CAM; CD54/ICAM-1 and CD29; p<0.05). The mean cardiomyocyte diameter (MCD) correlated highly significantly (p<0.01) with NCAM-AF, ICAM-1-AF, CD29-AF, CD18+ and TNFa+ infiltrates, and was associated less significantly (p<0.05) with CD3+, CD11a/LFA-1+, and CD11b/Mac-1+ infiltrates. In conclusion, NCAM-expression in ca. 50% of adult DCM hearts is associated with CMH, and may be induced by inflammatory pathways.