Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies.
OBJECTIVE
The ultrastructural features of the myocardium in arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been systematically investigated so far. The recent discovery of gene mutations encoding intercalated disc proteins prompted us to perform a transmission electron microscopy study on endomyocardial biopsies.


RESULTS
Twenty-one ARVC probands who fulfilled the international Task Force diagnostic criteria underwent right ventricular endomyocardial biopsy and screening of desmosome (D) protein encoding genes. Myocyte intercalated discs were analysed by transmission electron microscope and the data were compared with those of 10 controls and 10 patients with idiopathic dilated cardiomyopathy. Extensive fibro-fatty replacement with a residual myocardium of 59+/-23% was found in ARVC biopsy samples. Pathogenic D gene mutations were identified in 10 (48%): desmoglein-2 in four, desmoplakin in three and plakophilin-2 in three. Mean D length and D percent length of intercalated disc were significantly higher, D number was significantly lower and D gap was widened in ARVC. Moreover, abnormally located D in 75%, abnormal small junctions in 52%, and pale internal plaques in 32% of ARVC patients were found in the presence of a normal intercalated disc convolution index.


CONCLUSIONS
The ultrastructural evidence of intercalated discs remodelling in ARVC, together with the positive screening of D protein encoding genes in half of probands, are in keeping with an intercellular junction cardiomyopathy.
Basso
Cristina
C
Institute of Pathological Anatomy, University of Padua, Italy.
Czarnowska
Elzbieta
E
Della Barbera
Mila
M
Bauce
Barbara
B
Beffagna
Giorgia
G
Wlodarska
Elzbieta K
EK
Pilichou
Kalliopi
K
Ramondo
Angelo
A
Lorenzon
Alessandra
A
Wozniek
Olgierd
O
Corrado
Domenico
D
Daliento
Luciano
L
Danieli
Gian Antonio
GA
Valente
Marialuisa
M
Nava
Andrea
A
Thiene
Gaetano
G
Rampazzo
Alessandra
A
D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics / Q000473:pathology*; D001706:Biopsy / Q000379:methods; D002311:Cardiomyopathy, Dilated / Q000473:pathology; D051301:Desmoglein 2 / Q000235:genetics; D051180:Desmoplakins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000648:ultrastructure*; D051191:Plakophilins / Q000235:genetics; D012189:Retrospective Studies; D053782:Transforming Growth Factor beta3 / Q000235:genetics; D020257:Ventricular Remodeling
D051301:Desmoglein 2; D051180:Desmoplakins; C495337:PKP2 protein, human; D051191:Plakophilins; D053782:Transforming Growth Factor beta3