TNFa in myocardial ischemia/reperfusion, remodeling and heart failure
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Petra Kleinbongard • Rainer Schulz • Gerd Heusch
- چاپ و سال / کشور: 2010
Description
TNFa is crucially involved in the pathogenesis and progression of myocardial ischemia/reperfusion injury and heart failure. The formation and release of TNFa and its downstream signal transduction cascade following activation of its two receptor subtypes are characterized. Myocardial TNFa and TNF receptor activation have an ambivalent role in myocardial ischemia/reperfusion injury and protection from it. Excessive TNFa expression and subsequent cardiomyocyte TNF receptor type 1 stimulation induce contractile dysfunction, hypertrophy, fibrosis and cell death, while a lower TNFa concentration and subsequent cardiomyocyte TNF receptor type 2 stimulation are protective. Apart from its concentration and receptor subtype, the myocardial action of TNFa depends on the duration of its exposure and its localization. While detrimental during sustained ischemia, TNFa 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 TNFa in cardiovascular disease, notably heart failure, are critically discussed.
Heart Fail Rev (2011) 16:49–69 DOI 10.1007/s10741-010-9180-8 Published online: 23 June 2010
