Effects Of Cardiotrophin-1 On Cardiac Transcription Factor GATA-4 In Cardiac Hypertrophy

Objective: In overloaded heart the cardiomyocytes adapt to increased mechanical and neurohumoral stress by activation of hypertrophic program, resulting in morphological changes of individual cells and specific changes in gene expression. Thus, the understanding of the cellular and molecular changes leading to cardiomyocyte hypertrophy is a prerequisite for the treatment of cardiac hypertrophy and the subsequent prevention of heart failure. Accumulated evidences suggest a fundamental role of cardiac transcription factors especially the zinc finger transcription factor GATA-4 in hypertrophic agonist-induced cardiac hypertrophy, since it supports the basal and increased ventricular expression of genes encoding for various structural and contractile proteins during hypertrophy.However, the role of GATA-4 in Cardiotrophin-1 (CT-1), a novel IL-6 related cytokine, induced cardiomyocyte hypertrophy is not known. CT-1 is a more potent hypertrophy inducer than other known hypertrophic mediators. And the hypertrophy caused by CT-1 was distinct from that observed following G-protein-dependent stimulation, which may be more consistent with the eccentric hypertrophy produced by volume overload and more prone to convert into irreversible loss of cardiac function. The main purpose of the present experiment is to investigate whether CT-1 has effect on GATA-4 transcription and DNA binding activity.Methods: In this study, we investigated GATA-4 DNA binding activity and gene transcription in cultured hypertrophic cardiomyocytes induced by 10-12 mol/L, 10-11 mol/L, 10-10 mol/L, 10-9 mol/L or 10-8 mol/L CT-1 for 10 min, 15 min, 30 min, 1 h, 2 h, 3 h, 6 h, 12 h, 24 h or 48 h, as well as ANP gene expression and morphological changes in myocytes as...