Autonomous and growth factor-induced hypertrophy in cultured neonatal mouse cardiac myocytes - Comparison with rat

Cultured neonatal rat cardiac myocytes have been used extensively to study cellular and molecular mechanisms of cardiac hypertrophy. However, there ar e only a few studies in cultured mouse myocytes despite the increasing use of genetically engineered mouse models of cardiac hypertrophy. Therefore, w e characterized hypertrophic responses in low-density, serum-free cultures of neonatal mouse cardiac myocytes and compared them with rat myocytes. In mouse myocyte cultures, triiodothyronine (T3), norepinephrine (NE) through a beta -adrenergic receptor, and leukemia inhibitory factor induced hypertr ophy by a 20% to 30% increase in [H-3]phenylalanine-labeled protein content . T3 and NE also increased alpha -myosin heavy chain (MyHC) mRNA and reduce d beta -MyHC. In contrast, hypertrophic stimuli in rat myocytes, including alpha (1)-adrenergic agonists, endothelin-1, prostaglandin F-2 alpha interl eukin 1 beta, and phorbol 12-myristate 13-acetate (PMA), had no effect on m ouse myocyte protein content. In further contrast with the rat, none of the se agents increased atrial natriuretic factor or beta -MyHC mRNAs. Acute PM A signaling was intact by extracellular signal-regulated kinase (ERK1/2) an d immediate-early gene (fos/jun) activation. Remarkably, mouse but not rat myocytes had hypertrophy in the absence of added growth factors, with incre ases in cell area, protein content, and the mRNAs for atrial natriuretic fa ctor and beta -MyHC. We conclude that mouse myocytes have a unique autonomo us hypertrophy. On this background, T3, NE, and leukemia inhibitory factor activate hypertrophy with different mRNA phenotypes, but certain Gq- and pr otein kinase C-coupled agonists do not.