(Circulation. 1997;95:1247-1252.)
© 1997 American Heart Association, Inc.
Articles |
Tumor Necrosis Factor-
Provokes a Hypertrophic Growth Response in Adult Cardiac Myocytes
the Cardiology (T.Y., M.N., D.L.M.) and Cardiovascular Sciences (M.E.) Sections of the Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine, and Department of Immunology, University of Texas M.D. Anderson Center (J.L.B., B.W.M.), Houston.
Background Tumor necrosis factor-
(TNF-) is a pleiotropic cytokine with a broad range of concentration-dependent effects. The recent observation that TNF- is expressed by the cardiac myocyte after certain forms of stress suggests that TNF- might contribute to the maintenance of normal tissue homeostasis after environmental injury. Accordingly, the purpose of this study was to examine the effects of TNF- on protein synthesis in cultured adult cardiac myocytes.
Methods and Results Cultured adult feline cardiac myocytes were stimulated with 10 to 1000 U/mL TNF- to examine the effects of this cytokine on the rate of protein synthesis and degradation. Stimulation with TNF- led to an accelerated rate of general protein synthesis and a time-dependent decrease in protein degradation in adult cardiac myocytes. The specificity of these findings was demonstrated by studies in which the effects of TNF- on protein synthesis were blocked by a neutralizing anti–TNF- antibody as well as studies in which TNF-–conditioned medium had no effect on protein synthesis in myocytes. In addition to the TNF-–induced increase in the general protein synthesis, stimulation with TNF- led to a 2.4-fold increase in net actin protein synthesis and a 3.3-fold increase in net myosin heavy chain synthesis. Finally, the effects of TNF- on adult cardiac myocytes were shown to be dependent on cell-substrate interaction, suggesting that the cell signaling pathways used by TNF- are dependent on a preserved interaction between cell integrins and the extracellular matrix.
Conclusions The observation that TNF- provokes a hypertrophic growth response in cardiac myocytes suggests that TNF- may play an important role in myocardial homeostasis after environmental stress.
Key Words: myocytes • peptides • cells • hypertrophy • growth substances
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