Tumour necrosis factor-αcontributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia

Autor:	Gudrun H. Borchert, Libor Kopkan, František Kolář, Md. Abdul Hye Khan, P. Mandíková-Alánová, Jan Neckář, John D. Imig, A. Chytilová, Marketa Hlavackova
Rok vydání:	2015
Předmět:	Male medicine.medical_specialty Necrosis Physiology Myocardial Ischemia Nitric Oxide Synthase Type II medicine.disease_cause chemistry.chemical_compound Internal medicine medicine Animals Receptors Tumor Necrosis Factor Type II Rats Wistar Hypoxia chemistry.chemical_classification Reactive oxygen species biology Superoxide Dismutase Tumor Necrosis Factor-alpha business.industry Myocardium NF-kappa B Heart Hypoxia (medical) Malondialdehyde Adaptation Physiological Infliximab Rats Nitric oxide synthase Oxidative Stress Endocrinology chemistry Immunology biology.protein Tumor necrosis factor alpha Cyclooxygenase medicine.symptom business Oxidative stress
Zdroj:	Acta Physiologica. 214:97-108
ISSN:	1748-1708
DOI:	10.1111/apha.12489
Popis:	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.
Databáze:	OpenAIRE
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