© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Tumor necrosis factor in myocardial hypertrophy and ischaemia — an anti-apoptotic perspective
aHatter Institute for Cardiology Research, Cape Heart Centre, University of Cape Town Medical School, Cape Town, South Africa
bHeart Research Unit, Department of Medicine, University of Cape Town Medical School, Cape Town, South Africa
* Corresponding author. Tel.: +27-21-406-6358; fax: +27-21-447-8789 sack@samiot.uct.ac.za
Received 28 May 1999; accepted 16 July 1999
KEYWORDS Apoptosis; Cytokines; Hypertrophy; Remodelling; Ischemia; Myocytes
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1 Introduction |
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Tumour necrosis factor-alpha (TNF
) is a multifunctional cytokine that has been implicated as mediator of diverse physiologic and pathophysiologic events. These processes include inflammation, cellular survival, growth, differentiation and apoptosis. The local homeostatic cellular effects of cytokines may be considered ‘autocoid’ in nature. This word is derived from the Greek words autos (‘self’) and akos (‘remedy’), and refers to locally acting, biologically active agents, both peptides and non-peptides, that are distinct from neurotransmitters and hormones [1].
Recent studies have highlighted the pathogenic role of TNF in the development of myocardial disease, such as the direct correlation between serum TNF levels and the severity and progression of heart failure [2–4] and the development of myocarditis in mice that overexpress TNF specifically in the heart [5]. Taken together, these studies suggest that TNF is a mediator of cardiac pathology, acting at least in part via inflammatory pathways and via
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2 TNF — a prototypic pleiotropic cytokine
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3 TNF signalling pathways
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4 TNF production in the adult heart
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5 TNF and cardiac growth
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6 TNF modulation of cardiac contractile function and its role in myocardial ischaemia
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6.1 Preconditioning
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7 Bifunctional role for TNF
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7.1 Arguments from signalling pathways
7.2 Concentration-dependent effects
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8 Suppression of TNF release — therapeutic potentials/pitfalls
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9 Proposed hypothesis for future work |
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