PMID- 26679613
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1522-1601 (Electronic)
IS  - 0161-7567 (Linking)
VI  - 120
IP  - 4
DP  - 2016 Feb 15
TI  - Endothelin-1 mediates intermittent hypoxia-induced inflammatory vascular 
      remodeling through HIF-1 activation.
PG  - 437-43
LID - 10.1152/japplphysiol.00641.2015 [doi]
AB  - 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 Hif1alpha gene (HIF-1alpha(+/-)) 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-kappaB (NF-kappaB) 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-kappaB activity, and cytokine expression in the 
      aortic wall. This was accompanied by an increase in IMT. These modifications were 
      prevented in HIF-1alpha(+/-) 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-kappaB.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Gras, Emmanuelle
AU  - Gras E
AD  - Universite Grenoble Alpes, Laboratoire HP2, Grenoble, France; INSERM, U1042, 
      Grenoble, France; and.
FAU - Belaidi, Elise
AU  - Belaidi E
AD  - Universite Grenoble Alpes, Laboratoire HP2, Grenoble, France; INSERM, U1042, 
      Grenoble, France; and.
FAU - Briancon-Marjollet, Anne
AU  - Briancon-Marjollet A
AD  - Universite Grenoble Alpes, Laboratoire HP2, Grenoble, France; INSERM, U1042, 
      Grenoble, France; and.
FAU - Pepin, Jean-Louis
AU  - Pepin JL
AD  - Universite Grenoble Alpes, Laboratoire HP2, Grenoble, France; INSERM, U1042, 
      Grenoble, France; and CHU de Grenoble, Grenoble, France.
FAU - Arnaud, Claire
AU  - Arnaud C
AUID- ORCID: 0000-0003-0964-9423
AD  - Universite Grenoble Alpes, Laboratoire HP2, Grenoble, France; INSERM, U1042, 
      Grenoble, France; and.
FAU - Godin-Ribuot, Diane
AU  - Godin-Ribuot D
AUID- ORCID: 0000-0001-7589-932X
AD  - Universite Grenoble Alpes, Laboratoire HP2, Grenoble, France; INSERM, U1042, 
      Grenoble, France; and diane.ribuot@univ-grenoble-alpes.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151217
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Cytokines)
RN  - 0 (Endothelin-1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Animals
MH  - Aorta/metabolism/physiopathology
MH  - Carotid Intima-Media Thickness
MH  - Cytokines/metabolism
MH  - Endothelin-1/*metabolism
MH  - Hypertension/metabolism/physiopathology
MH  - Hypoxia/metabolism/*physiopathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Inflammation/*metabolism/*physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Sleep Apnea, Obstructive/metabolism/physiopathology
MH  - Vascular Remodeling/*physiology
OTO - NOTNLM
OT  - endothelin-1
OT  - hypoxia inducible factor-1
OT  - inflammation
OT  - intermittent hypoxia
OT  - nuclear factor-kappaB
OT  - vascular remodeling
EDAT- 2015/12/19 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/12/19 06:00
PHST- 2015/07/28 00:00 [received]
PHST- 2015/12/16 00:00 [accepted]
PHST- 2015/12/19 06:00 [entrez]
PHST- 2015/12/19 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - japplphysiol.00641.2015 [pii]
AID - 10.1152/japplphysiol.00641.2015 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2016 Feb 15;120(4):437-43. doi: 
      10.1152/japplphysiol.00641.2015. Epub 2015 Dec 17.