Epithelial sodium channels in endothelial cells mediate diet-induced endothelium stiffness and impaired vascular relaxation in obese female mice.
Animals
Diet
/ adverse effects
Diet, Western
Endothelial Cells
/ metabolism
Epithelial Sodium Channels
/ genetics
Epithelium
/ metabolism
Mice
Mice, Knockout
Muscle, Smooth, Vascular
Nitric Oxide
/ metabolism
Nitric Oxide Synthase Type III
/ metabolism
Obesity
/ metabolism
Sirtuin 1
/ metabolism
Vascular Stiffness
/ drug effects
Vasodilation
Endothelial sodium channels
Endothelial stiffness
Fuel sensing kinases
Nitric oxide
Obesity
Oxidative stress
Journal
Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
08
07
2019
accepted:
10
07
2019
pubmed:
16
7
2019
medline:
12
2
2020
entrez:
15
7
2019
Statut:
ppublish
Résumé
Mineralocorticoid receptor activation of the epithelial sodium channel in endothelial cells (ECs) (EnNaC) is accompanied by aldosterone induced endothelial stiffening and impaired nitric oxide (NO)-mediated arterial relaxation. Recent data support enhanced activity of the alpha subunit of EnNaC (αEnNaC) mediates this aldosterone induced endothelial stiffening and associated endothelial NO synthase (eNOS) activation. There is mounting evidence that diet induced obesity diminishes expression and activation of AMP-activated protein kinase α (AMPKα), sirtuin 1 (Sirt1), which would be expected to lead to impaired downstream eNOS activation. Thereby, we posited that enhanced EnNaC activation contributes to diet induced obesity related increases in stiffness of the endothelium and diminished NO mediated vascular relaxation by increasing oxidative stress and related inhibition of AMPKα, Sirt1, and associated eNOS inactivation. Sixteen to twenty week-old αEnNaC knockout (αEnNaC Enhanced EnNaC activation-mediated WD-induced increases in sodium currents in isolated lung ECs, increased endothelial stiffness and impaired aortic endothelium-dependent relaxation to acetylcholine (10 These data suggest that endothelial specific EnNaC activation mediates WD-induced endothelial stiffness, impaired eNOS activation, aortic fibrosis and remodeling through increased aortic oxidative stress and increased inflammation related to a reduction of AMPKα and Sirt 1 mediated eNOS phosphorylation/activation and NO production.
Identifiants
pubmed: 31302199
pii: S0026-0495(19)30143-X
doi: 10.1016/j.metabol.2019.153946
pmc: PMC6901094
mid: NIHMS1544119
pii:
doi:
Substances chimiques
Epithelial Sodium Channels
0
Nitric Oxide
31C4KY9ESH
Nitric Oxide Synthase Type III
EC 1.14.13.39
Nos3 protein, mouse
EC 1.14.13.39
Sirt1 protein, mouse
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
57-66Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL073101
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL132012
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL085119
Pays : United States
Organisme : BLRD VA
ID : I01 BX003391
Pays : United States
Organisme : BLRD VA
ID : I01 BX001981
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL107910
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
Metabolism. 2019 Mar;92:82-97
pubmed: 30502373
Metabolism. 2017 Jul;72:120-143
pubmed: 28641779
Hypertension. 2013 May;61(5):1053-9
pubmed: 23460285
Metabolism. 2019 Feb;91:18-29
pubmed: 30468782
Mol Cell Endocrinol. 2011 Jan 1;331(1):102-8
pubmed: 20797423
J Biol Chem. 2011 Sep 16;286(37):32444-53
pubmed: 21795700
Hypertension. 2019 Feb;73(2):458-468
pubmed: 30624990
Metabolism. 2018 Jan;78:69-79
pubmed: 28920862
Endocrinology. 2013 Oct;154(10):3632-42
pubmed: 23885014
Hypertension. 2013 Dec;62(6):1105-10
pubmed: 24060894
Front Physiol. 2017 Jun 30;8:456
pubmed: 28713285
Steroids. 2010 Aug-Sep;75(8-9):544-9
pubmed: 19778545
Cell Rep. 2017 Oct 24;21(4):1009-1020
pubmed: 29069584
Hypertension. 2009 Jun;53(6):1048-53
pubmed: 19433780
Hypertension. 2015 Jul;66(1):99-107
pubmed: 26015449
Hypertension. 2008 Nov;52(5):777-86
pubmed: 18852392
Hypertension. 2015 Mar;65(3):531-9
pubmed: 25489061
PLoS One. 2017 Sep 26;12(9):e0185319
pubmed: 28950003
J Mol Cell Cardiol. 2014 Dec;77:42-52
pubmed: 25268649
J Biol Chem. 2003 Aug 22;278(34):31629-39
pubmed: 12791703
Circ Res. 2016 Mar 18;118(6):935-943
pubmed: 26879229
Nitric Oxide. 2013 Aug 1;32:29-35
pubmed: 23583951
Hypertension. 2018 Sep;72(3):537-548
pubmed: 29987104
Oxid Med Cell Longev. 2017;2017:7543973
pubmed: 28546854
J Biol Chem. 2013 Mar 22;288(12):8136-45
pubmed: 23362276
J Physiol. 2013 Mar 1;591(5):1277-93
pubmed: 23297302
Circ Res. 2009 Feb 27;104(4):496-505
pubmed: 19131647
Metabolism. 2018 May;82:36-46
pubmed: 29289515
Circ Res. 2010 Apr 2;106(6):1117-28
pubmed: 20167927
Hypertension. 2003 May;41(5):1096-101
pubmed: 12707286
J Am Coll Cardiol. 2012 May 15;59(20):1771-7
pubmed: 22575315
Hypertension. 2019 Feb;73(2):273-281
pubmed: 30580685
J Cell Sci. 2016 Jan 15;129(2):290-7
pubmed: 26621031
Cardiovasc Res. 2017 Jul 1;113(9):1055-1063
pubmed: 28838041
Metabolism. 2019 Mar;92:98-107
pubmed: 30399375
Microcirculation. 2009 Apr;16(3):276-87
pubmed: 19225981
Hypertension. 2000 Nov;36(5):878-84
pubmed: 11082160
Cardiorenal Med. 2012 Aug;2(3):200-210
pubmed: 22969776
Eur Heart J. 2013 Dec;34(45):3515-24
pubmed: 23594590
Front Immunol. 2017 Jul 21;8:842
pubmed: 28785264
Oncotarget. 2016 Nov 8;7(45):72458-72468
pubmed: 27776344
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14855-60
pubmed: 17785417
Hypertension. 2019 Apr;73(4):849-858
pubmed: 30827147
Metabolism. 2018 Oct;87:123-135
pubmed: 29679615
Hypertension. 2018 Sep;72(3):731-738
pubmed: 29987101
Circulation. 2009 Mar 31;119(12):1643-52
pubmed: 19289642
Biochem Pharmacol. 2013 May 1;85(9):1288-96
pubmed: 23422569
J Endocrinol. 2017 Jul;234(1):T67-T82
pubmed: 28634267
PLoS One. 2012;7(7):e41520
pubmed: 22844486
Circulation. 2010 Feb 2;121(4):505-11
pubmed: 20083680