TNF-α signaling: TACE inhibition to put out the burning heart

被引：11

作者：

Dittrich, Gesine M. ^{[1
]}

Heineke, Joerg ^{[1
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, European Ctr Angiosci ECAS, Dept Cardiovasc Physiol, Mannheim, Germany

来源：

PLOS BIOLOGY | 2020年 / 18卷 / 12期

关键词：

NECROSIS-FACTOR-ALPHA; FAILURE; DYSFUNCTION; ENDOTOXIN; THERAPY;

D O I：

10.1371/journal.pbio.3001037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

More than 20 years ago, Seta and colleagues hypothesized that cytokines, which are activated by myocardial injury, significantly drive heart failure progression and would therefore be effective targets to treat cardiac dysfunction. Unfortunately, several clinical trials inhibiting key cytokines like tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (Il-1 beta) turned out negative or even revealed adverse clinical effects. Providing a potential mechanistic explanation for the ineffectiveness of TNF-alpha blockade in heart failure, novel findings demonstrate that the membrane-bound precursor form of TNF-alpha, transmembrane TNF-alpha (tmTNF-alpha), mediates cardioprotective effects during pressure overload-induced cardiac remodeling. This study suggests that preventing tmTNF-alpha cleavage by targeting the TNF-alpha converting enzyme (TACE) rather than inhibiting TNF-alpha signaling altogether might be a valuable therapeutic approach.

引用

页数：4

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