Current Molecular Medicine

David W. Li  
College of Medicine
University of Nebraska Medical Center
Omaha, NE
USA

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Inflammatory Mediators and the Failing Heart: A Translational Approach

Author(s): Abhinav Diwan, Tony Tran, Arunima Misra and Douglas L. Mann

Affiliation: Winters Center for Heart Failure Research, MS 524, 6565 Fannin, Houston, Texas 77030, USA

Abstract:

Recent studies have identified the importance of proinflammatory mediators in regulating cardiac structure in health and disease. Recent studies suggest that cytokines that are expressed within the myocardium in response to a environmental injury, namely tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and the interleukin-6 (IL-6) family of cytokines play an important role in initiating and integrating homeostatic responses within the heart. However, these “stress-activated” cytokines all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. Indeed, there is now a growing appreciation that these molecules may play an important role in mediating disease progression in the failing heart. The growing appreciation of the pathophysiological consequences of sustained expression of proinflammatory mediators in pre-clinical and clinical heart failure models culminated in a series of multicenter clinical trials that utilized “targeted” approaches to neutralize tumor necrosis factor (TNF) 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. MeSH-Medline keywords: [110] congestive heart failure, [147] growth factors / cytokines, tumor necrosis factor, inflammatory mediators, clinical trial, etanercept, infliximab.

Keywords: proinflammatory mediators, myocardium, tumor necrosis factor (TNF), congestive heart failure, infliximab, cytokines

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Article Details

VOLUME: 3
ISSUE: 2
Page: [161 - 182]
Pages: 22
DOI: 10.2174/1566524033361537
Price: $58