Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation

Objectives: Recent in vivo and in vitro studies in animals have demonstrated that cytokines of the IL-6 family are involved in cardiac hypertrophy and in protection of cardiomyocytes against apoptosis. The present study aims to analyse the capacity Of human atrial cardiac cells (i.e., cardiomyocytes and fibroblasts) to display the gp130 receptor subunit, and to evaluate its functionality. Methods: Twenty human atrial biopsies were used for immunohistochemistry, in situ hybridisation, and western blot analysis or dissociated for isolation and primary culture of cardiac cells. Results: Fibroblasts present in tissue or maintained in primary culture clearly express gp130 whereas the signal in cardiomyocytes is weaker. Culture of cardiac cells with a gp130 agonist antibody enhances atrial natriuretic peptide (ANP), beta myosin heavy chain (beta-MHC) expression in cardiomyocytes, and significantly increases the cell Surface area (mum(2)). This process could involve STAT3 (signal transducer and activator of transcription 3) phosphorylation. Conclusions: These results demonstrate that gp130 activation in human cardiac cells leads to cardiomyocyte hypertrophy. We discuss several hypotheses on the role of IL-6-type cytokines on cardiomyocyte functions. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.