Circulation Research. 2002;91:988-998
doi: 10.1161/01.RES.0000043825.01705.1B
doi: 10.1161/01.RES.0000043825.01705.1B
© 2002 American Heart Association, Inc.
Review |
Inflammatory Mediators and the Failing Heart
Past, Present, and the Foreseeable Future
From the Winters Center for Heart Failure Research, the Cardiology Section, Department of Medicine, Veterans Administration Medical Center, Methodist Hospital, and Baylor College of Medicine, Houston, Tex.
Correspondence to Douglas L. Mann, MD, Winters Center for Heart Failure Research, MS 524, 6565 Fannin, Houston, TX 77030. E-mail dmann{at}bcm.tmc.edu
Recent studies have identified the importance of proinflammatory mediators in the development and progression of heart failure. The growing appreciation of the pathophysiological consequences of sustained expression of proinflammatory mediators in preclinical and clinical heart failure models culminated in a series of multicenter clinical trials that used "targeted" approaches to neutralize tumor necrosis factor in patients with moderate to advanced heart failure. However, these targeted approaches have resulted in worsening heart failure, thereby raising a number of important questions about what role, if any, proinflammatory cytokines play in the pathogenesis of heart failure. This review will summarize the tremendous growth of knowledge that has taken place in this field, with a focus on what we have learned from the negative clinical trials, as well as the potential direction of future research in this area.
Key Words: tumor necrosis factor • inflammatory mediators • clinical trial • etanercept • infliximab
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A. Diwan, Z. Dibbs, S. Nemoto, G. DeFreitas, B. A. Carabello, N. Sivasubramanian, E. M. Wilson, F. G. Spinale, and D. L. Mann Targeted Overexpression of Noncleavable and Secreted Forms of Tumor Necrosis Factor Provokes Disparate Cardiac Phenotypes Circulation, January 20, 2004; 109(2): 262 - 268. [Abstract] [Full Text] [PDF]
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 R. Marfella, K. Esposito, M. Siniscalchi, F. Cacciapuoti, F. Giugliano, D. Labriola, M. Ciotola, C. Di Palo, L. Misso, and D. Giugliano Effect of Weight Loss on Cardiac Synchronization and Proinflammatory Cytokines in Premenopausal Obese Women Diabetes Care, January 1, 2004; 27(1): 47 - 52. [Abstract] [Full Text] [PDF]
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K. C Wollert and H. Drexler Growth hormone and proinflammatory cytokine activation in heart failure: Just a new verse to an old sirens' song? Eur. Heart J., December 2, 2003; 24(24): 2164 - 2165. [Full Text] [PDF]
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S. S.-l. Li, C.-w. Cheng, C.-l. Fu, Y.-h. Chan, M.-p. Lee, J. W.-m. Chan, and S.-f. Yiu Left Ventricular Performance in Patients With Severe Acute Respiratory Syndrome: A 30-Day Echocardiographic Follow-Up Study Circulation, October 14, 2003; 108(15): 1798 - 1803. [Abstract] [Full Text] [PDF]
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B. I. Jugdutt Ventricular Remodeling After Infarction and the Extracellular Collagen Matrix: When Is Enough Enough? Circulation, September 16, 2003; 108(11): 1395 - 1403. [Full Text] [PDF]
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P.B. Massion, O. Feron, C. Dessy, and J.-L. Balligand Nitric Oxide and Cardiac Function: Ten Years After, and Continuing Circ. Res., September 5, 2003; 93(5): 388 - 398. [Abstract] [Full Text] [PDF]
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 L. B. Ware, X. Fang, and M. A. Matthay Protein C and thrombomodulin in human acute lung injury Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L514 - L521. [Abstract] [Full Text] [PDF]
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M. Tanno, R. Bassi, D. A. Gorog, A. T. Saurin, J. Jiang, R. J. Heads, J. L. Martin, R. J. Davis, R. A. Flavell, and M. S. Marber Diverse Mechanisms of Myocardial p38 Mitogen-Activated Protein Kinase Activation: Evidence for MKK-Independent Activation by a TAB1-Associated Mechanism Contributing to Injury During Myocardial Ischemia Circ. Res., August 8, 2003; 93(3): 254 - 261. [Abstract] [Full Text] [PDF]
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H. Nakamura, S. Umemoto, G. Naik, G. Moe, S. Takata, P. Liu, and M. Matsuzaki Induction of left ventricular remodeling and dysfunction in the recipient heart after donor heart myocardial infarction: new insights into the pathologic role of tumor necrosis factor-alpha from a novel heterotopic transplant-coronary ligation rat model J. Am. Coll. Cardiol., July 2, 2003; 42(1): 173 - 181. [Abstract] [Full Text] [PDF]
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X. He, Y. Liu, V. Sharma, R. T. Dirksen, R. Waugh, S.-S. Sheu, and W. Min ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes Am. J. Pathol., July 1, 2003; 163(1): 243 - 251. [Abstract] [Full Text] [PDF]
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 K. J. Kelly Distant Effects of Experimental Renal Ischemia/Reperfusion Injury J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1549 - 1558. [Abstract] [Full Text] [PDF]
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C.-s. Liang, A. Yatani, Y. Himura, M. Kashiki, and S. Y. Stevens Desipramine attenuates loss of cardiac sympathetic neurotransmitters produced by congestive heart failure and NE infusion Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1729 - H1736. [Abstract] [Full Text] [PDF]
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