title: Effects of rosiglitazone and interactions with growth-regulating factors in ventricular cell hypertrophy.
abstract: Chronic administration of thiazolidinediones might predispose to cardiac hypertrophy. The aim was to investigate direct effects of rosiglitazone in rat ventricular cardiomyocytes maintained in vitro (24 h). Rosiglitazone (< or =10(-5) M) did not increase protein synthesis and produced small inconsistent increases in cellular protein. In the presence of serum (10% v/v), but not insulin-like growth factor (IGF-1, 10(-8) M) or insulin (1 U/ml), an interaction with rosiglitazone to stimulate protein synthesis was observed. The hypertrophic responses to noradrenaline (5x10(-6) M), PMA (10(-7) M) and ET-1 (10(-7) M) were not attenuated by rosiglitazone. Rosiglitazone (10(-7) M) did not influence protein synthesis in response to insulin (1 U/ml) and elevated glucose (2.5x10(-2) M) alone or in combination, but attenuated the increase in protein mass observed in response to elevated glucose alone. In re-differentiated cardiomyocytes, a model of established hypertrophy, rosiglitazone (10(-8) M-10(-6) M) increased protein synthesis. Together, these data indicate that rosiglitazone does not initiate cardiomyocyte hypertrophy directly in vitro. However, during chronic administration, the interaction of rosiglitazone with locally-derived growth-regulating factors may make a modest contribution to cardiac remodelling and influence the extent of compensatory hypertrophy of the compromised rat heart.
authors.affiliation: Department of Therapeutics and Pharmacology, Cardioendocrine Research Group, Centre for Cardiovascular Research, The School of Medicine, The Queen's University of Belfast, Northern Ireland, UK. d.bell@qub.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: McDermott
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019332:Endothelin-1 / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D016895:Culture Media, Serum-Free; D019332:Endothelin-1; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine