Tumour necrosis factor-α contributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25760892
DOI
10.1111/apha.12489
Knihovny.cz E-resources
- Keywords
- chronic hypoxia, ischaemia/reperfusion injury, reactive oxygen species, tumour necrosis factor-α,
- MeSH
- Adaptation, Physiological physiology MeSH
- Hypoxia metabolism MeSH
- Infliximab pharmacology MeSH
- Myocardial Ischemia metabolism MeSH
- Rats MeSH
- Myocardium metabolism MeSH
- NF-kappa B metabolism MeSH
- Oxidative Stress drug effects MeSH
- Rats, Wistar MeSH
- Receptors, Tumor Necrosis Factor, Type II metabolism MeSH
- Heart drug effects MeSH
- Superoxide Dismutase metabolism MeSH
- Nitric Oxide Synthase Type II metabolism MeSH
- Tumor Necrosis Factor-alpha antagonists & inhibitors metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Infliximab MeSH
- NF-kappa B MeSH
- Receptors, Tumor Necrosis Factor, Type II MeSH
- Superoxide Dismutase MeSH
- Nitric Oxide Synthase Type II MeSH
- Tumor Necrosis Factor-alpha MeSH
AIM: It has been demonstrated that tumour necrosis factor-alpha (TNF-α) via its receptor 2 (TNFR2) plays a role in the cardioprotective effects of preconditioning. It is also well known that chronic hypoxia is associated with activation of inflammatory response. With this background, we hypothesized that TNF-α signalling may contribute to the improved ischaemic tolerance of chronically hypoxic hearts. METHODS: Adult male Wistar rats were kept either at room air (normoxic controls) or at continuous normobaric hypoxia (CNH; inspired O2 fraction 0.1) for 3 weeks; subgroups of animals were treated with infliximab (monoclonal antibody against TNF-α; 5 mg kg(-1), i.p., once a week). Myocardial levels of oxidative stress markers and the expression of selected signalling molecules were analysed. Infarct size (tetrazolium staining) was assessed in open-chest rats subjected to acute coronary artery occlusion/reperfusion. RESULTS: CNH increased myocardial TNF-α level and expression of TNFR2; this response was abolished by infliximab treatment. CNH reduced myocardial infarct size from 50.8 ± 4.3% of the area at risk in normoxic animals to 35.5 ± 2.4%. Infliximab abolished the protective effect of CNH (44.9 ± 2.0%). CNH increased the levels of oxidative stress markers (3-nitrotyrosine and malondialdehyde), the expression of nuclear factor κB and manganese superoxide dismutase, while these effects were absent in infliximab-treated animals. CNH-elevated levels of inducible nitric oxide synthase and cyclooxygenase 2 were not affected by infliximab. CONCLUSION: TNF-α plays a role in the induction of ischaemia-resistant cardiac phenotype of CNH rats, possibly via the activation of protective redox signalling.
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Sixty Years of Heart Research in the Institute of Physiology of the Czech Academy of Sciences
