Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation.
OBJECTIVE
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 microm(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.
Ancey
Cecile
C
Laboratoire des Biomembranes et Signalisation Cellulaire, UMR CNRS 6558, Université de Poitiers, 40 avenue du recteur Pineau, 86022 Poitiers Cedex, France.
Menet
Emmanuelle
E
Corbi
Pierre
P
Fredj
Sandra
S
Garcia
Martine
M
Rücker-Martin
Catherine
C
Bescond
Jocelyn
J
Morel
Franck
F
Wijdenes
John
J
Lecron
Jean-Claude
JC
Potreau
Daniel
D
D000368:Aged; D000704:Analysis of Variance; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D051777:AraC Transcription Factor; D009320:Atrial Natriuretic Factor / Q000032:analysis; D001426:Bacterial Proteins; D015153:Blotting, Western / Q000379:methods; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D048429:Cell Size; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006325:Heart Atria; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000032:analysis; D010766:Phosphorylation; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D018121:Receptors, Cytokine / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D012097:Repressor Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors
D019138:Antibodies, Blocking; D015703:Antigens, CD; D051777:AraC Transcription Factor; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D000644:Quaternary Ammonium Compounds; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C456339:cytokine receptor, GLM-R; D050822:Cytokine Receptor gp130; C034730:zwittergent 3-12; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains