The role of tumor necrosis factor alpha in the pathophysiology of congestive heart failure.
A variety of clinical and experimental investigations have suggested that tumor necrosis factor alpha (TNF-alpha) may play a role in the pathophysiology of heart failure. Serum levels of TNF-alpha are elevated in patients with heart failure, and both cardiac and infiltrating cells of the myocardium can produce this proinflammatory cytokine. Both cardiac myocytes and nonmyocytes also express receptors for TNF-alpha, and experimental studies on isolated cells, muscles, and transgenic models demonstrate the ability of TNF-alpha to recapitulate functional and biochemical alterations resembling that observed in human congestive heart failure. The intracellular pathways affected by TNF-alpha include production of ceramide and an alteration in calcium metabolism. Recent studies in both animal models and clinical investigations suggest that anti-TNF-alpha therapies may limit the pathophysiologic consequences of congestive heart failure.
McTiernan
C F
CF
Cardiovascular Institute, University of Pittsburgh, Biomedical Science Tower 1744.1, 200 Lothrop Street, Pittsburgh, PA 15213, USA. mctiernanc@msx.upmc.edu
Feldman
A M
AM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D015536:Down-Regulation; D000068800:Etanercept; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D009206:Myocardium / Q000166:cytology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept