Heterogeneous loss of connexin43 protein in nonischemic dilated cardiomyopathy with ventricular tachycardia.
BACKGROUND
Gap junction alterations recently have been implicated in chronic heart failure, but direct evidence between gap junction manifestation in nonischemic dilated cardiomyopathy (DCM) is lacking. The current study examines whether qualitative changes or altered distribution of gap junctional connexin43 (Cx43) are related to global ventricular function and ventricular arrhythmia in DCM.


RESULTS
We investigated 31 DCM patients (52 +/- 15 years) and 5 control subjects (55 +/- 10 years). Expression of Cx43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy in right ventricular biopsy specimens from each patient. The expression level of Cx43 protein was defined as the proportion of tissue area occupied by Cx43 (percent tissue area) in each test area. Cx43 immunoreactive signal expressed as percent tissue area was not correlated with the change in left ventricular ejection fraction (P = 0.17). Of 31 DCM patients, 23% subsequently developed sustained ventricular tachycardia (VT), which allowed retrospective division of the samples into two groups: non-VT and VT. Left ventricular ejection fraction was comparable in both groups, but the percent tissue area in the VT groups was significantly decreased compared with that of the non-VT groups (P = 0.03). Furthermore, Cx43 protein was distributed heterogeneously in the VT groups (P < 0.0001).


CONCLUSIONS
Heterogeneous reduction of Cx43 protein may result in development of malignant ventricular arrhythmia in DCM.
Kitamura
Hidetsuna
H
Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Ohnishi
Yoshio
Y
Yoshida
Akihiro
A
Okajima
Katsunori
K
Azumi
Hiroshi
H
Ishida
Akihiko
A
Galeano
Erdulfo J
EJ
Kubo
Shinya
S
Hayashi
Yoshitake
Y
Itoh
Hiroshi
H
Yokoyama
Mitsuhiro
M
D000328:Adult; D000368:Aged; D006328:Cardiac Catheterization; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018031:Connexin 43 / Q000096:biosynthesis* / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D005455:Fluorescent Antibody Technique; D018740:Genetic Heterogeneity; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D013223:Statistics as Topic; D013318:Stroke Volume / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology
D018031:Connexin 43