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±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.
Department of Cardiology and Pneumonology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Karsten
K
Ostermann
Department of Cardiology and Pneumonology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; IKDT (Institut für kardiale Diagnostik und Therapie), Moltkestrasse 31, Berlin, Germany.
Heinz-Peter
HP
Schultheiss
Department of Cardiology and Pneumonology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; Department of Cardiology, Pneumonology and Intensive Care Medicine, Clinic for Internal Medicine I, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany. Electronic address: michel.noutsias@uni-jena.de.
Michel
M
Noutsias
D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics
D019006:Neural Cell Adhesion Molecules
Cell adhesion molecules; Cytokines; Digital image analysis; Dilated cardiomyopathy; Endomyocardial biopsies; Hypertrophy; Immunohistochemistry; Inflammation; Inflammatory cardiomyopathy; NCAM; Neural cell adhesion molecule; TNF