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Mediators Inflamm. 2015;2015:620258. doi: 10.1155/2015/620258. Epub 2015 Mar 19.

Toll-like receptor-4 mediated inflammation is involved in the cardiometabolic alterations induced by intermittent hypoxia.

Author information

1
Université Grenoble Alpes, Laboratoire HP2, 38042 Grenoble, France ; INSERM U1042, 38042 Grenoble, France.
2
Université de Rouen, UFR Médecine-Pharmacie, 76183 Rouen, France ; INSERM U1096, 76183 Rouen, France.
3
Université Grenoble Alpes, Laboratoire HP2, 38042 Grenoble, France ; INSERM U1042, 38042 Grenoble, France ; CHU, Hôpital A. Michallon, Laboratoires du Sommeil et EFCR, 38043 Grenoble, France.
4
Université Grenoble Alpes, Laboratoire HP2, 38042 Grenoble, France ; INSERM U1042, 38042 Grenoble, France ; CHU, Hôpital A. Michallon, Pôle Pluridisciplinaire de Médecine, 38043 Grenoble, France.

Abstract

OBJECTIVE:

Intermittent hypoxia (IH) is a major component of sleep apnea syndrome as its cardiometabolic complications have been mainly attributed to IH. The pathophysiology is still poorly understood but there are some similarities with the obesity-associated cardiometabolic complications. As the latter results from inflammation involving toll-like receptor-4 (TLR4) signaling, we assessed this pathway in the cardiometabolic consequences of IH.

METHODS:

Lean adult male TLR4-deficient (TLR4(-/-)) mice and their controls (C57BL/6 mice) were exposed to either IH (FiO2 21-5%, 1 min cycle, 8 h/day) or air (normoxic mice) for 4 weeks. Animals were assessed at 1-week exposure for insulin tolerance test and after 4-week exposure for morphological and inflammatory changes of the epididymal fat and thoracic aorta.

RESULTS:

IH induced insulin resistance, morphological and inflammatory changes of the epididymal fat (smaller pads and adipocytes, higher release of TNF-α and IL-6) and aorta (larger intima-media thickness and higher NFκB-p50 activity). All these alterations were prevented by TLR4 deletion.

CONCLUSION:

IH induces metabolic and vascular alterations that involve TLR4 mediated inflammation. These results confirm the important role of inflammation in the cardiometabolic consequences of IH and suggest that targeting TLR4/NFκB pathway could represent a further therapeutic option for sleep apnea patients.

PMID:
25873766
PMCID:
PMC4383499
DOI:
10.1155/2015/620258
[Indexed for MEDLINE]
Free PMC Article

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