On the role of the gap junction protein Cx43 (GJA1) in human cardiac malformations with Fallot-pathology. a study on paediatric cardiac specimen.

INTRODUCTION: Gap junction channels are involved in growth and differentiation. Therefore, we wanted to elucidate if the main cardiac gap junction protein connexin43 (GJA1) is altered in patients with Tetralogy of Fallot or double-outlet right ventricle of Fallot-type (62 patients referred to as Fallot) compared to other cardiac anomalies (21 patients referred to as non-Fallot). Patients were divided into three age groups: 0-2years, 2-12years and >12years. Myocardial tissue samples were collected during corrective surgery and analysis of cell morphology, GJA1- and N-cadherin (CDH2)-distribution, as well as GJA1 protein- and mRNA-expression was carried out. Moreover, GJA1-gene analysis of 16 patients and 20 healthy subjects was performed. RESULTS: Myocardial cell length and width were significantly increased in the oldest age group compared to the younger ones. GJA1 distribution changed significantly during maturation with the ratio of polar/lateral GJA1 increasing from 2.93±0.68 to 8.52±1.41. While in 0-2years old patients ∼6% of the lateral GJA1 was co-localised with CDH2 this decreased with age. Furthermore, the changes in cell morphology and GJA1-distribution were not due to the heart defect itself but were significantly dependent on age. Total GJA1 protein expression decreased during growing-up, whereas GJA1-mRNA remained unchanged. Sequencing of the GJA1-gene revealed only few heterozygous single nucleotide polymorphisms within the Fallot and the healthy control group. CONCLUSION: During maturation significant changes in gap junction remodelling occur which might be necessary for the growing and developing heart. In our study point mutations within the Cx43-gene could not be identified as a cause of the development of TOF.

[Expression of the heat shock protein-70 in the myocardial cells of cyanosis congenital heart diseases].

OBJECTIVE: To evaluate the expression and myocardial protection of heat shock protein-70 (HSP70) in the myocardial cells of cyanosis congenital heart diseases. METHODS: The study enrolled 24 patients with congenital heart disease: 12 cases of non-cyanosis (group A), and the other 12 cases of cyanosis (group B). During the operation the samples of myocardium in the right atrium were attained at 0 min ischemia, 20 min ischemia, and 20 min reperfusion. They were used to evaluate the content of HSP70 by immunohistochemistry and activation of SOD and content of MDA by chemochromatometry. RESULTS: The content of HSP70 in myocardial cells during the operation was not significantly different in both groups (P > 0. 05). The content of HSP70 significantly decreased in group B compared with that of group A (P <0.05). The activity of SOD significantly decreased and the content of MDA significantly increased in group B during the operation (P < 0.05). CONCLUSION: Decreased expression of HSP70 is associated with the decreased tolerance to ischemia-reperfusion injury in myocardial cells of cyanosis congenital heart disease.