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1551588 
Journal Article 
TNF alpha in myocardial ischemia/reperfusion, remodeling and heart failure 
Kleinbongard, P; Schulz, R; Heusch, G 
2011 
Yes 
Heart Failure Reviews
ISSN: 1382-4147
EISSN: 1573-7322 
16 
1 
49-69 
20571888 
WOS:000285750000006 
TNF alpha is crucially involved in the pathogenesis and
progression of myocardial ischemia/reperfusion injury and heart failure. The formation and
release of TNF alpha and its downstream signal transduction cascade following activation of its
two receptor subtypes are characterized. Myocardial TNF alpha and TNF receptor activation have an
ambivalent role in myocardial ischemia/reperfusion injury and protection from it. Excessive TNF
alpha expression and subsequent cardiomyocyte TNF receptor type 1 stimulation induce contractile
dysfunction, hypertrophy, fibrosis and cell death, while a lower TNF alpha concentration and
subsequent cardiomyocyte TNF receptor type 2 stimulation are protective. Apart from its
concentration and receptor subtype, the myocardial action of TNF alpha depends on the duration of
its exposure and its localization. While detrimental during sustained ischemia, TNF alpha
contributes to ischemic preconditioning protection, no matter whether it is the first, second or
third window of protection, and both TNF receptors are involved in the protective signal
transduction cascade. Finally, the available clinical attempts to antagonize TNF alpha in
cardiovascular disease, notably heart failure, are critically discussed. 
Cardioprotection; Fibrosis; Heart failure; Hypertrophy; Myocardial function; Myocardial ischemia; Remodeling; Reperfusion; Tumor necrosis factor alpha