Tumour necrosis factor-α contributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25760892
DOI
10.1111/apha.12489
Knihovny.cz E-zdroje
- Klíčová slova
- chronic hypoxia, ischaemia/reperfusion injury, reactive oxygen species, tumour necrosis factor-α,
- MeSH
- fyziologická adaptace fyziologie MeSH
- hypoxie metabolismus MeSH
- infliximab farmakologie MeSH
- ischemická choroba srdeční metabolismus MeSH
- krysa rodu Rattus MeSH
- myokard metabolismus MeSH
- NF-kappa B metabolismus MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- receptory TNF - typ II metabolismus MeSH
- srdce účinky léků MeSH
- superoxiddismutasa metabolismus MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- TNF-alfa antagonisté a inhibitory metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- infliximab MeSH
- NF-kappa B MeSH
- receptory TNF - typ II MeSH
- superoxiddismutasa MeSH
- synthasa oxidu dusnatého, typ II MeSH
- TNF-alfa 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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