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Endothelin-1 mediates intermittent hypoxia-induced inflammatory vascular remodeling through HIF-1 activation
- Source :
- Journal of Applied Physiology. 120:437-443
- Publication Year :
- 2016
- Publisher :
- American Physiological Society, 2016.
-
Abstract
- Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality, and apnea-induced intermittent hypoxia (IH) is known to promote various cardiovascular alterations such as vascular remodeling. However, the mechanisms that underlie IH remain incompletely investigated. We previously demonstrated that the hypoxia-inducible factor-1 (HIF-1) and endothelin-1 (ET-1) are involved in arterial hypertension and myocardial susceptibility to infarction induced by IH. Thus the objective of the present study was to investigate whether both ET-1 and HIF-1 were also involved in the vascular inflammatory remodeling induced by IH. Mice partially deficient for the Hif1α gene (HIF-1α+/−) and their wild-type equivalents, as well as C57BL/6J mice, treated or not with bosentan, a dual endothelin receptor antagonist, were exposed to IH or normoxia for 2 wk, 8 h/day. Splenocyte proliferative and secretory capacities, aortic nuclear factor-κB (NF-κB) and HIF-1 activities, and expression of cytokines and intima-media thickness (IMT) were measured. IH induced a systemic and aortic inflammation characterized by an increase in splenocyte proliferative and secretory capacities, aortic NF-κB activity, and cytokine expression in the aortic wall. This was accompanied by an increase in IMT. These modifications were prevented in HIF-1α+/− and bosentan-treated mice. The results of this study suggest that ET-1 is a major contributor to the vascular inflammatory remodeling induced by OSA-related IH, probably through HIF-1-dependent activation of NF-κB.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Physiology
Inflammation
Vascular Remodeling
030204 cardiovascular system & hematology
Carotid Intima-Media Thickness
Mice
03 medical and health sciences
0302 clinical medicine
Physiology (medical)
Internal medicine
medicine.artery
medicine
Splenocyte
Animals
Hypoxia
Aorta
Sleep Apnea, Obstructive
Endothelin-1
Endothelin receptor antagonist
business.industry
NF-kappa B
Intermittent hypoxia
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Endothelin 1
Bosentan
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
Hypertension
Cytokines
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 15221601 and 87507587
- Volume :
- 120
- Database :
- OpenAIRE
- Journal :
- Journal of Applied Physiology
- Accession number :
- edsair.doi.dedup.....560121e23bfe73aeb46ad7f378dc0d55