PMID- 26739492
OWN - NLM
STAT- MEDLINE
DCOM- 20160725
LR  - 20220331
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 310
IP  - 6
DP  - 2016 Mar 15
TI  - Intermittent hypoxia induces NF-kappaB-dependent endothelial activation via 
      adipocyte-derived mediators.
PG  - C446-55
LID - 10.1152/ajpcell.00240.2015 [doi]
AB  - Aberrant release of adipocytokines from adipose tissues dysregulates 
      cardiometabolic functions. The present study hypothesizes that chronic 
      intermittent hypoxia (IH) present in obstructive sleep apnea leads to adipose 
      tissue dysfunction, which in turn contributes to vascular pathogenesis. The 
      effect of IH was evaluated in adipose depots and aortic tissues in lean rats in 
      vivo. Furthermore, the cellular and molecular mechanisms underlying 
      pathophysiological interactions between adipocytes and endothelial cells were 
      investigated in vitro. The in vivo results showed that IH induced upregulation of 
      IL-6 and monocyte chemoattractant protein-1 (MCP-1) in subcutaneous and 
      periaortic adipose tissues and downregulated phosphorylation of endothelial 
      nitric oxide synthase [eNOS (ser1177)] in the aorta with activation of Erk and 
      p38 MAPK. In support, cultured adipocytes demonstrated IH-induced elevations of 
      NADPH oxidase 4, phosphorylation of Erk, NF-kappaBp65, and inducible NOS (iNOS) and 
      increased expression of IL-6 and MCP-1. Likewise, endothelial EA.hy926 (EA) cells 
      exposed to IH showed eNOS (ser1177) and intracellular cGMP reduction, whereas 
      MCP-1 and iNOS expression were upregulated. Treatment of EA cells with 
      conditioned media derived from IH-exposed cultured adipocytes caused nuclear 
      translocation of NF-kappaBp65 and elevation of MCP-1, which were prevented by 
      addition of neutralizing IL-6 antibodies to the conditioned media. Recombinant 
      IL-6 in addition to IH induced further MCP-1 release and iNOS protein expression 
      in EA cells, which were prevented by pharmacological inhibition of Erk, p38, and 
      NF-kappaB. These findings suggest that IH could induce adipose tissue inflammation, 
      which may cross talk with endothelial cells via adipocyte-derived mediators such 
      as IL-6, and promote NF-kappaB-dependent endothelial dysfunction.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Lee, Mary Y K
AU  - Lee MY
AD  - Division of Respiratory Medicine, Department of Medicine, Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong, Hong Kong; Research Centre of Heart, 
      Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University 
      of Hong Kong, Hong Kong.
FAU - Wang, Yan
AU  - Wang Y
AD  - Division of Respiratory Medicine, Department of Medicine, Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong, Hong Kong;
FAU - Mak, Judith C W
AU  - Mak JC
AD  - Division of Respiratory Medicine, Department of Medicine, Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong, Hong Kong; Research Centre of Heart, 
      Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University 
      of Hong Kong, Hong Kong.
FAU - Ip, Mary S M
AU  - Ip MS
AD  - Division of Respiratory Medicine, Department of Medicine, Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong, Hong Kong; Research Centre of Heart, 
      Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University 
      of Hong Kong, Hong Kong msmip@hku.hk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160106
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adipocytes/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Endothelial Cells/*metabolism
MH  - Hypoxia/*metabolism
MH  - Inflammation/metabolism
MH  - Inflammation Mediators/*metabolism
MH  - Interleukin-6/metabolism
MH  - MAP Kinase Signaling System/physiology
MH  - Male
MH  - NADPH Oxidases/metabolism
MH  - NF-kappa B/*metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Phosphorylation/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/physiology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - NF-kappaB
OT  - adipose inflammation
OT  - endothelial function
OT  - intermittent hypoxia
EDAT- 2016/01/08 06:00
MHDA- 2016/07/28 06:00
CRDT- 2016/01/08 06:00
PHST- 2015/08/17 00:00 [received]
PHST- 2016/01/06 00:00 [accepted]
PHST- 2016/01/08 06:00 [entrez]
PHST- 2016/01/08 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
AID - ajpcell.00240.2015 [pii]
AID - 10.1152/ajpcell.00240.2015 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2016 Mar 15;310(6):C446-55. doi: 
      10.1152/ajpcell.00240.2015. Epub 2016 Jan 6.