Volume 10 (2005) pp 287-303 |
Abstract |
Abnormalities in the expression and distribution of Connexin 43
(Cx43) in cardiomyocytes may lead to anomalous conotruncal embryogenesis
and disturbances in the maturation and function of the heart. Tetralogy of Fallot
(TOF) is the most frequent, cyanotic congenital heart defect in which
conotruncal anomalies, right ventricle dysfunction and life-threatening
arrhythmias occur. In this study, age-related changes in the expression and
spatial distribution of Cx43 in cardiomyocytes from TOF children compared to
patients without right ventricular outflow tract pathology were determined
Confocal microscopy and flow cytometry were used to assess the changes.
Disturbances in both the expression and distribution of Cx43 were found. In the
group of infants with TOF, a lower level of expression of the protein was
determined. Cardiomyocytes from TOF hearts were found to have Cx43
distributed over their entire surface, which is the pattern seen in immature tissue.
In the controls, Cx43 was located within the intercalated disks. Expression of
Cx43 in TOF hearts increases with the age of the subject, whereas its spatial
distribution remains the same in both infants and older children. Disturbances in
Cx43 expression and localization may influence heart embryogenesis and
maturation, contribute to hypertrophy and dysfunction of the right ventricle and
induce arrhythmias in children with TOF. Early redistribution of Cx43 and functional maturation of the heart muscle support a strategy of early total
correction of the defect. |
Address and Contact Information |
1Department of Pediatric Cardiac Surgery, Polish-American Children's Hospital,
Collegium Medicum, Jagiellonian University, Wielicka 265, 30-663 Krakółw,
Poland, 2Department of Cell Biology, Faculty of Biotechnology, Jagiellonian
University, Gronostajowa 7, 30-387 Kraków, Poland, 3Department of
Immunology, Faculty of Biotechnology, Jagiellonian University, Gronostajowa
7, 30-387 Kraków, Poland, 4Department of Biophysics, Laboratory of Confocal
Microscopy and Image Analysis, Jagiellonian University, Gronostajowa 7,
30-387 Kraków, Poland * Corresponding author, tel: 0048 12 658 10 23, fax: 0048 12 657 39 47,
e-mail: mimalec@cyf-kr.edu.pl |