JP-2 gene expression affects excitation-contraction coupling in the dilated cardiomyopathy heart failure / 中华胸心血管外科杂志

ABSTRACT

ObjectiveHeart failure is closely associated with a defected calcium-induced calcium release (CICR) between the transverse tubular (TT) invagination of plasma membrane and terminal cistemae of sarcoplasmic reticulum (SR) in cardiac myocytes.The underlying cause of this defect is not well understood.Any factors impacting the TT and SR connecting may reduce the excitation-contraction coupling efficiency.Junctophilin 2 (Jph 2) is a cardiac protein anchoring SR to TT.This research is to explore the JP-2 expression in the cardiomyopathy heart failure myocytes.Objective Myocardium specimens of the lateral segments of left ventricule were collected from cardiomyopathy heart failure patients and the transplantation donors.MethodsGroup Aheart failure cases diagnosised as cardiomyopathy and samples were collected from the left ventricle lateral wall.Group Bcontrol samples from the transplantation donors which not used for the recepients reason.Electron microscopy technique was used to test the mean junctional distance between TT and SR.Westernblot technique was used to test the Junctophilin 2 expression and the RT-PCR method was used to test the JP-2 gene expression.The data were analysises with the SPSS 12.0 software,P ＜ 0.05 was accepted as different significantly.ResultsSamples were collected from 14 patients with severe heart failure and 6 control cases.Electron microscopy ultrastructure results showed in an average 100 μm2 of the myocardial cells area the coupling numbers of the control group and heart failure group were 60 and 112 (P ＜0.001 ).The electrical micrography mean junctional distance between TT and SR was significantly increased from the control group ( 16.2 ± 3.2) nm to the ( 19.3 ±4.3 ) am in the heart failure group( P ＜0.001 ) ). The Westernblot results showed Junctophilin 2 versus GAPDH expression down regulated in the heart failure group comparing to the control group (7.2％ vs 15.3 ％,P ＜ 0.05 ).The RT-PCR implied the JP-2 gene versus GAPDH expression also down regulated in the heart failure group comparing to the control group (37.5％ vs 98.8％,P ＜ 0.01 ).ConclusionConclusion JP-2 gene down-regulation may be one of the earliest change in the heart failure molecular mechanisms.