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Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes.

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TLDR
IL-1 beta caused myocyte hypertrophy associated with induction of fetal genes (ANF and beta-MHC) and downregulation of three important calcium regulatory genes (SERCA2, CRC, and VDCC) and may contribute to the abnormal structural and functional alterations of cardiac myocytes in conditions marked by mononuclear cell infiltration.
Abstract
Mononuclear cell infiltration and local cytokine elaboration are hallmarks of inflammatory and immunologic heart diseases. To test the hypothesis that cytokines can modulate cardiac myocyte growth and phenotype, myocytes cultured from neonatal rat hearts were exposed to IL-1 beta, an inflammatory cytokine prevalent in myocardial inflammation. IL-1 beta (2 ng/ml, 24 h) increased [3H]leucine incorporation by 30 +/- 4% (P 10-fold, n = 4), and decreased mRNA levels for sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) (-46 +/- 7%; P < 0.001; n = 11), calcium release channel (CRC) (-65 +/- 11%, P < 0.001, n = 8) and voltage-dependent calcium channel (VDCC) (-53 +/- 7%, P < 0.001, n = 8). NG-monomethyl-L-arginine (1 mM), an inhibitor of nitric oxide (NO) synthesis, did not inhibit the IL-1 beta-induced protein synthesis or changes in mRNA levels. In ventricular myocardium obtained from adult rats treated with lipopolysaccharide (4 mg/kg intraperitoneally 18 h) to stimulate systemic cytokine production, there were changes in the mRNA levels for beta-MHC (6 +/- 1-fold, P < 0.01, n = 4), SERCA2 (-65 +/- 4%, P < 0.0001, n = 4), CRC (-67 +/- 5%, P < 0.001, n = 4), and VDCC (-58 +/- 5%, P < 0.001; n = 4) that were qualitatively similar to those observed in cultured myocytes. Thus, IL-1 beta, acting via an NO-independent mechanism, caused myocyte hypertrophy associated with induction of fetal genes (ANF and beta-MHC) and downregulation of three important calcium regulatory genes (SERCA2, CRC, and VDCC). IL-1 beta may contribute to the abnormal structural and functional alterations of cardiac myocytes in conditions marked by mononuclear cell infiltration.

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Inhibitory Effects of Antioxidants on Neonatal Rat Cardiac Myocyte Hypertrophy Induced by Tumor Necrosis Factor-α and Angiotensin II

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Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts.

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Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype.

TL;DR: The phenotypic changes of cardiac cells in response to Ang II in vitro closely mimic those of growth factor response in vitro and of load-induced hypertrophy in vivo, and all biological effects of Ang II examined here are mediated primarily by the AT1 receptors.
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Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload

TL;DR: Results suggest that induction of cellular protooncogenes and heat shock (stress) protein genes is an early response to pressure overload, whereas reinduction of the genes normally expressed only in perinatal life, such as fetal isoforms of contractile proteins and atrial natriuretic factor, is a later event.
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