Title of article :
The role of tumor necrosis factor in the pathophysiology of heart failure
Author/Authors :
Arthur M. Feldman، نويسنده , , Alain Combes، نويسنده , , H. Daniel Wagner، نويسنده , , Toshiaki Kadakomi، نويسنده , , Toru Kubota، نويسنده , , Yun You Li، نويسنده , , Charles McTiernan، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2000
Abstract :
Recent studies have focused their attention on the role of the proinflammatory cytokine tumor necrosis factor (TNF) in the development of heart failure. First recognized as an endotoxin-induced serum factor that caused necrosis of tumors and cachexia, it is now recognized that TNF participates in the pathophysiology of a group of inflammatory diseases including rheumatoid arthritis and Crohn’s disease. The normal heart does not express TNF; however, the failing heart produces robust quantities. Furthermore, there is a direct relationship between the level of TNF expression and the severity of disease. In addition, both in vivo and in vitro studies demonstrate that TNF effects cellular and biochemical changes that mirror those seen in patients with congestive heart failure. Furthermore, in animal models, the development of the heart failure phenotype can be abrogated at least in part by anticytokine therapy. Based on information from experimental studies, investigators are now evaluating the clinical efficacy of novel anticytokine and anti-TNF strategies in patients with heart failure; one such strategy is the use of a recombinantly produced chimeric TNF alpha soluble receptor. Thus, in view of the emerging importance of proinflammatory cytokines in the pathogenesis of heart disease, we review the biology of TNF, its role in inflammatory diseases, the effects of TNF on the physiology of the heart and the development of clinical strategies that target the cytokine pathways.
Keywords :
endothelial leukocyte adhesion molecules , tumor necrosis factor , ICAMS , TNFR , intracellular adhesion molecules , soluble tumor necrosis factor receptor , IL-1 , interleukin-1 , Lipopolysaccharide , alpha-MHC , MCP , alpha myosin heavy chain , monocyte chemoattractant protein , AMP , mRNA , adenosine monophosphate , Messenger RNA , beta-MHC , NYHA , CHF , SERCA , Congestive heart failure , sarcoplasmic reticulum Ca2+ ATPase , ELAMS , TNF , beta myosin heavy chain , New York Heart Association , LPS
Journal title :
JACC (Journal of the American College of Cardiology)
Journal title :
JACC (Journal of the American College of Cardiology)