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(Circulation. 1996;93:704-711.)
© 1996 American Heart Association, Inc.
Articles |
Tumor Necrosis Factor-
and Tumor Necrosis Factor Receptors in the Failing Human Heart
From the Cardiology Section of the Department of Medicine, Veterans Administration Medical Center, and Baylor College of Medicine, Houston, Tex; and the Cardiology Section of the Department of Medicine, University of Colorado, Denver (R.D.B.).
Background Tumor necrosis factor-
(TNF-) is a
proinflammatory cytokine that produces negative inotropic
effects in the heart. Recently, elevated levels of TNF- have been
reported in patients with advanced congestive heart failure. Although
TNF- is thought to exert its deleterious effects by binding to two
cell surface receptors, TNFR1 and TNFR2, the level of expression and
regulation of TNF receptors in the heart in cardiac disease states is
not known.
Methods and Results We examined mRNA and protein levels for
TNFR1, TNFR2, and TNF- in explanted hearts from organ donors as well
as in patients with end-stage dilated
cardiomyopathy (DCM) and ischemic heart
disease (IHD). Northern blot analysis revealed that mRNA for
TNFR1 and TNFR2 was present in nonfailing, DCM, and IHD hearts.
TNFR1 and TNFR2 receptor protein levels, as measured by ELISA, were
decreased 60% in DCM and IHD patients compared with nonfailing hearts
(P<.005). To determine a potential mechanism for the
decrease in TNF receptor expression, we measured levels of circulating
soluble TNF receptors (sTNFRs) in DCM and IHD patients. This
analysis showed that there was a significant
one-and-a-half to threefold increase in sTNFRs in DCM
(P<.03) and IHD patients (P<.001). Another
important finding was that TNF- mRNA and TNF- protein were
present in the explanted hearts from DCM and IHD patients but not
in nonfailing hearts.
Conclusions In summary, the results of this study
constitute the initial demonstration that TNF receptor proteins are
dynamically regulated in patients with advanced congestive heart
failure. Moreover, the observation that failing hearts express elevated
levels of TNF- suggests that overexpression of this cytokine
may be one of several different maladaptive mechanisms responsible for
the progressive cardiac decompensation that occurs in advanced heart
failure.
Key Words: cells, tumor necrosis factor- • receptors • heart failure
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H. Oral, N. Sivasubramanian, D. B. Dyke, R. H. Mehta, P. M. Grossman, K. Briesmiester, W. P. Fay, F. D. Pagani, S. F. Bolling, D. L. Mann, et al. Myocardial Proinflammatory Cytokine Expression and Left Ventricular Remodeling in Patients With Chronic Mitral Regurgitation Circulation, February 18, 2003; 107(6): 831 - 837. [Abstract] [Full Text] [PDF]
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B. London, L. C. Baker, J. S. Lee, V. Shusterman, B.-R. Choi, T. Kubota, C. F. McTiernan, A. M. Feldman, and G. Salama Calcium-dependent arrhythmias in transgenic mice with heart failure Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H431 - H441. [Abstract] [Full Text] [PDF]
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P. C. Schulze, J. Kratzsch, A. Linke, N. Schoene, V. Adams, S. Gielen, S. Erbs, S. Moebius-Winkler, and G. Schuler Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure Eur J Heart Fail, January 1, 2003; 5(1): 33 - 40. [Abstract] [Full Text] [PDF]
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C. Steenbergen, C. A. Afshari, J. G. Petranka, J. Collins, K. Martin, L. Bennett, A. Haugen, P. Bushel, and E. Murphy Alterations in apoptotic signaling in human idiopathic cardiomyopathic hearts in failure Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H268 - H276. [Abstract] [Full Text] [PDF]
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R. J. Scheubel, M. Tostlebe, A. Simm, S. Rohrbach, R. Prondzinsky, F. N. Gellerich, R.-E. Silber, and J. Holtz Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression J. Am. Coll. Cardiol., December 18, 2002; 40(12): 2174 - 2181. [Abstract] [Full Text] [PDF]
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V.M. Conraads, P. Beckers, J. Bosmans, L.S. De Clerck, W.J. Stevens, C.J. Vrints, and D.L. Brutsaert Combined endurance/resistance training reduces plasma TNF-{alpha} receptor levels in patients with chronic heart failure and coronary artery disease Eur. Heart J., December 1, 2002; 23(23): 1854 - 1860. [Abstract] [Full Text] [PDF]
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D. L. Mann Inflammatory Mediators and the Failing Heart: Past, Present, and the Foreseeable Future Circ. Res., November 29, 2002; 91(11): 988 - 998. [Abstract] [Full Text] [PDF]
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J. R. R. Heyen, E. R. Blasi, K. Nikula, R. Rocha, H. A. Daust, G. Frierdich, J. F. Van Vleet, P. De Ciechi, E. G. McMahon, and A. E. Rudolph Structural, functional, and molecular characterization of the SHHF model of heart failure Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1775 - H1784. [Abstract] [Full Text] [PDF]
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Y. Chen, J. H. Traverse, R. Du, M. Hou, and R. J. Bache Nitric Oxide Modulates Myocardial Oxygen Consumption in the Failing Heart Circulation, July 9, 2002; 106(2): 273 - 279. [Abstract] [Full Text] [PDF]
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T. Saito, F. Hu, L. Tayara, L. Fahas, H. Shennib, and A. Giaid Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H339 - H345. [Abstract] [Full Text] [PDF]
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G. Plenz, H. Eschert, M. Erren, T. Wichter, M. Bohm, M. Flesch, H. H. Scheld, and M. C. Deng The interleukin-6/interleukin-6-receptorsystem is activated in donor hearts J. Am. Coll. Cardiol., May 1, 2002; 39(9): 1508 - 1512. [Abstract] [Full Text] [PDF]
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A. Goette, U. Lendeckel, and H. U Klein Signal transduction systems and atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 247 - 258. [Abstract] [Full Text] [PDF]
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A. Yndestad, J. Kristian Damas, H. Geir Eiken, T. Holm, T. Haug, S. Simonsen, S. S. Froland, L. Gullestad, and P. Aukrust Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure Cardiovasc Res, April 1, 2002; 54(1): 175 - 182. [Abstract] [Full Text] [PDF]
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W. S. Bradham, B. Bozkurt, H. Gunasinghe, D. Mann, and F. G. Spinale Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective Cardiovasc Res, March 1, 2002; 53(4): 822 - 830. [Abstract] [Full Text] [PDF]
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S. Adamopoulos, J. Parissis, D. Karatzas, C. Kroupis, M. Georgiadis, G. Karavolias, J. Paraskevaidis, K. Koniavitou, A. J. S. Coats, and D. T. Kremastinos Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fasligand system in patients with chronic heart failure J. Am. Coll. Cardiol., February 20, 2002; 39(4): 653 - 663. [Abstract] [Full Text] [PDF]
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R. Kell, A. Haunstetter, T.J. Dengler, C. Zugck, W. Kubler, and M. Haass Do cytokines enable risk stratification to be improved in NYHA functional class III patients?. Comparison with other potential predictors of prognosis Eur. Heart J., January 1, 2002; 23(1): 70 - 78. [Abstract] [Full Text] [PDF]
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P. O. Iversen, P. R. Woldbaek, T. Tonnessen, and G. Christensen Decreased hematopoiesis in bone marrow of mice with congestive heart failure Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R166 - R172. [Abstract] [Full Text] [PDF]
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A.L. Clark, M. Loebe, E.V. Potapov, K. Egerer, C. Knosalla, R. Hetzer, and S.D. Anker Ventricular assist device in severe heart failure. Effects on cytokines, complement and body weight Eur. Heart J., December 2, 2001; 22(24): 2275 - 2283. [Abstract] [PDF]
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P. Razeghi, M. Mukhopadhyay, T. J. Myers, J. N. Williams, C. S. Moravec, O. H. Frazier, and H. Taegtmeyer Myocardial tumor necrosis factor-{alpha} expression does not correlate with clinical indices of heart failure in patients on left ventricular assist device support Ann. Thorac. Surg., December 1, 2001; 72(6): 2044 - 2050. [Abstract] [Full Text] [PDF]
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C.-W. Kong, T.-G. Hsu, F.-J. Lu, W.-L. Chan, and K. Tsai Leukocyte mitochondria depolarization and apoptosis in advanced heart failure: clinical correlations and effect of therapy J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1693 - 1700. [Abstract] [Full Text] [PDF]
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P. O. Iversen, G. Nicolaysen, and M. Sioud DNA enzyme targeting TNF-alpha mRNA improves hemodynamic performance in rats with postinfarction heart failure Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2211 - H2217. [Abstract] [Full Text] [PDF]
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S. Adamopoulos, J. T. Parissis, and D. Th. Kremastinos A glossary of circulating cytokines in chronic heart failure Eur J Heart Fail, October 1, 2001; 3(5): 517 - 526. [Abstract] [Full Text] [PDF]
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J. Marin-Garcia, M. J. Goldenthal, and G. W. Moe Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure Cardiovasc Res, October 1, 2001; 52(1): 103 - 110. [Abstract] [Full Text] [PDF]
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T. Kadokami, C. Frye, B. Lemster, C. L. Wagner, A. M. Feldman, and C. F. McTiernan Anti-Tumor Necrosis Factor-{alpha} Antibody Limits Heart Failure in a Transgenic Model Circulation, September 4, 2001; 104(10): 1094 - 1097. [Abstract] [Full Text] [PDF]
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