NOX1 mediates metabolic heart disease in mice and is upregulated in monocytes of humans with diastolic dysfunction.
Diastolic dysfunction
Hypertrophy
Inflammation
Metabolic heart disease
NOX1
Journal
Cardiovascular research
ISSN: 1755-3245
Titre abrégé: Cardiovasc Res
Pays: England
ID NLM: 0077427
Informations de publication
Date de publication:
10 11 2022
10 11 2022
Historique:
received:
25
07
2021
accepted:
19
11
2021
pubmed:
2
12
2021
medline:
15
11
2022
entrez:
1
12
2021
Statut:
ppublish
Résumé
Microvascular inflammation plays an important role in the pathogenesis of diastolic dysfunction (DD) and metabolic heart disease. NOX1 is expressed in vascular and immune cells and has been implicated in the vascular pathology of metabolic disease. However, its contribution to metabolic heart disease is less understood. NOX1-deficient mice (KO) and male wild-type (WT) littermates were fed a high-fat high-sucrose diet (HFHS) and injected streptozotocin (75 mg/kg i.p.) or control diet (CTD) and sodium citrate. Despite similar weight gain and increase in fasting blood glucose and insulin, only WT-HFHS but not KO-HFHS mice developed concentric cardiac hypertrophy and elevated left ventricular filling pressure. This was associated with increased endothelial adhesion molecule expression, accumulation of Mac-2-, IL-1β-, and NLRP3-positive cells and nitrosative stress in WT-HFHS but not KO-HFHS hearts. Nox1 mRNA was solidly expressed in CD45+ immune cells isolated from healthy mouse hearts but was negligible in cardiac CD31+ endothelial cells. However, in vitro, Nox1 expression increased in response to lipopolysaccharide (LPS) in endothelial cells and contributed to LPS-induced upregulation of Icam-1. Nox1 was also upregulated in mouse bone marrow-derived macrophages in response to LPS. In peripheral monocytes from age- and sex-matched symptomatic patients with and without DD, NOX1 was significantly higher in patients with DD compared to those without DD. NOX1 mediates endothelial activation and contributes to myocardial inflammation and remodelling in metabolic disease in mice. Given its high expression in monocytes of humans with DD, NOX1 may represent a potential target to mitigate heart disease associated with DD.
Identifiants
pubmed: 34849611
pii: 6443118
doi: 10.1093/cvr/cvab349
pmc: PMC9648822
doi:
Substances chimiques
Lipopolysaccharides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2973-2984Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
Déclaration de conflit d'intérêts
Conflict of interest: none declared.
Références
JAMA. 2020 Jun 23;323(24):2526-2528
pubmed: 32573660
Circulation. 2005 Oct 25;112(17):2677-85
pubmed: 16246966
Circ Res. 2001 May 11;88(9):888-94
pubmed: 11348997
Circulation. 2007 Jun 26;115(25):3213-23
pubmed: 17592090
J Card Fail. 2014 Dec;20(12):984-95
pubmed: 25225111
Eur Heart J. 2015 Jul 14;36(27):1718-27, 1727a-1727c
pubmed: 25888006
Stroke. 2005 May;36(5):1040-6
pubmed: 15845888
Eur Heart J. 2014 Oct 21;35(40):2797-815
pubmed: 25104786
Circ Res. 2017 Aug 18;121(5):502-511
pubmed: 28684629
JACC Heart Fail. 2016 Apr;4(4):312-24
pubmed: 26682792
Nature. 1999 Sep 2;401(6748):79-82
pubmed: 10485709
Nat Immunol. 2019 Jan;20(1):29-39
pubmed: 30538339
J Biol Chem. 2009 Dec 18;284(51):35403-11
pubmed: 19850916
Immunity. 2014 Jan 16;40(1):91-104
pubmed: 24439267
PLoS One. 2011 Feb 07;6(2):e14665
pubmed: 21326871
Circ Heart Fail. 2016 Sep;9(9):
pubmed: 27609832
BMC Endocr Disord. 2014 Feb 01;14:9
pubmed: 24484869
Clin Sci (Lond). 2016 Aug 1;130(15):1363-74
pubmed: 27190136
Biomarkers. 2020 Mar;25(2):201-211
pubmed: 32063068
JACC Heart Fail. 2018 Jan;6(1):1-7
pubmed: 29284577
Eur Heart J. 2016 Jul 14;37(27):2129-2200
pubmed: 27206819
J Biol Chem. 2016 Sep 16;291(38):20030-41
pubmed: 27489105
Free Radic Biol Med. 2005 Aug 1;39(3):381-91
pubmed: 15993337
BMJ Open. 2019 Jun 5;9(6):e028408
pubmed: 31171553
J Mol Cell Cardiol. 2018 Jan;114:20-28
pubmed: 29055654
PLoS One. 2013 Apr 11;8(4):e60931
pubmed: 23593350
Physiol Rev. 2007 Jan;87(1):245-313
pubmed: 17237347
Neth Heart J. 2016 Apr;24(4):275-86
pubmed: 26936157
FEBS Lett. 2006 Jan 23;580(2):497-504
pubmed: 16386251
Nat Rev Endocrinol. 2016 Mar;12(3):144-53
pubmed: 26678809
Clin Cardiol. 2017 Sep;40(9):626-632
pubmed: 28475816
Circ Res. 2001 Feb 2;88(2):E14-22
pubmed: 11157681
Cell Metab. 2013 Jun 4;17(6):860-872
pubmed: 23747245
Exp Cell Res. 2004 Nov 1;300(2):455-62
pubmed: 15475009
JACC Heart Fail. 2014 Oct;2(5):489-99
pubmed: 25194285
Circulation. 2013 May 7;127(18):1888-902
pubmed: 23564668
Nature. 1986 Apr 3-9;320(6061):454-6
pubmed: 3007998
Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):9056-61
pubmed: 15941833
Gastroenterology. 2019 Mar;156(4):1156-1172.e6
pubmed: 30445007
Diabetologia. 2012 Jul;55(7):2069-79
pubmed: 22549734
Science. 2008 May 2;320(5876):674-7
pubmed: 18403674
Steroids. 2019 Dec;152:108494
pubmed: 31518594
J Card Fail. 2016 Dec;22(12):1023-1027
pubmed: 27697502
J Am Coll Cardiol. 2013 Jul 23;62(4):263-71
pubmed: 23684677
Eur Heart J. 2019 Oct 21;40(40):3297-3317
pubmed: 31504452
Hypertension. 2008 Feb;51(2):500-6
pubmed: 18195161
Blood. 2016 Dec 22;128(25):2960-2975
pubmed: 27737891
Sci Signal. 2016 Nov 01;9(452):ra105
pubmed: 27803283
J Clin Invest. 2011 Jun;121(6):2111-7
pubmed: 21633179
Redox Biol. 2019 Feb;21:101063
pubmed: 30576919