Faculty Collaboration Database

Tumour necrosis factor-α contributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia. Acta Physiol (Oxf) 2015 May;214(1):97-108

Date

03/12/2015

Pubmed ID

25760892

DOI

10.1111/apha.12489

Scopus ID

2-s2.0-84927615290 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

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.

Author List

Chytilová A, Borchert GH, Mandíková-Alánová P, Hlaváčková M, Kopkan L, Khan MA, Imig JD, Kolář F, Neckář J

MESH terms used to index this publication - Major topics in bold

Adaptation, Physiological
Animals
Heart
Hypoxia
Infliximab
Male
Myocardial Ischemia
Myocardium
NF-kappa B
Nitric Oxide Synthase Type II
Oxidative Stress
Rats
Rats, Wistar
Receptors, Tumor Necrosis Factor, Type II
Superoxide Dismutase
Tumor Necrosis Factor-alpha