| First Author | Poulain L | Year | 2015 |
| Journal | Mediators Inflamm | Volume | 2015 |
| Pages | 620258 | PubMed ID | 25873766 |
| Mgi Jnum | J:238256 | Mgi Id | MGI:5818656 |
| Doi | 10.1155/2015/620258 | Citation | Poulain L, et al. (2015) Toll-like receptor-4 mediated inflammation is involved in the cardiometabolic alterations induced by intermittent hypoxia. Mediators Inflamm 2015:620258 |
| abstractText | 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-alpha and IL-6) and aorta (larger intima-media thickness and higher NFkappaB-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/NFkappaB pathway could represent a further therapeutic option for sleep apnea patients. |
