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

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 ± 19 years; 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.