Endothelial PHD2 deficiency induces nitrative stress
Animals
Humans
Mice
Caveolin 1
/ genetics
Lung
/ metabolism
Pulmonary Arterial Hypertension
/ genetics
Reactive Nitrogen Species
/ metabolism
Reactive Oxygen Species
/ metabolism
Vascular Remodeling
/ genetics
Nitrosative Stress
/ genetics
Hypoxia-Inducible Factor-Proline Dioxygenases
/ genetics
Disease Models, Animal
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
19
04
2020
accepted:
24
06
2022
pubmed:
8
7
2022
medline:
27
12
2022
entrez:
7
7
2022
Statut:
epublish
Résumé
Nitrative stress is a characteristic feature of the pathology of human pulmonary arterial hypertension. However, the role of nitrative stress in the pathogenesis of obliterative vascular remodelling and severe pulmonary arterial hypertension remains largely unclear. Our recently identified novel mouse model ( Nitrative stress was markedly elevated whereas endothelial caveolin-1 (Cav1) expression was suppressed in the lungs of These data suggest that suppression of Cav1 expression secondary to PHD2 deficiency augments nitrative stress through endothelial nitric oxide synthase activation, which contributes to obliterative vascular remodelling and severe pulmonary hypertension. Thus, a reactive oxygen/nitrogen species scavenger might have therapeutic potential for the inhibition of obliterative vascular remodelling and severe pulmonary arterial hypertension.
Sections du résumé
BACKGROUND
Nitrative stress is a characteristic feature of the pathology of human pulmonary arterial hypertension. However, the role of nitrative stress in the pathogenesis of obliterative vascular remodelling and severe pulmonary arterial hypertension remains largely unclear.
METHOD
Our recently identified novel mouse model (
RESULTS
Nitrative stress was markedly elevated whereas endothelial caveolin-1 (Cav1) expression was suppressed in the lungs of
CONCLUSION
These data suggest that suppression of Cav1 expression secondary to PHD2 deficiency augments nitrative stress through endothelial nitric oxide synthase activation, which contributes to obliterative vascular remodelling and severe pulmonary hypertension. Thus, a reactive oxygen/nitrogen species scavenger might have therapeutic potential for the inhibition of obliterative vascular remodelling and severe pulmonary arterial hypertension.
Identifiants
pubmed: 35798360
pii: 13993003.02643-2021
doi: 10.1183/13993003.02643-2021
pmc: PMC9791795
pii:
doi:
Substances chimiques
Caveolin 1
0
Reactive Nitrogen Species
0
Reactive Oxygen Species
0
Egln1 protein, mouse
EC 1.14.11.29
Hypoxia-Inducible Factor-Proline Dioxygenases
EC 1.14.11.29
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL140409
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL164014
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148810
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133951
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL158596
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL138278
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL162299
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright ©The authors 2022.
Déclaration de conflit d'intérêts
Conflict of interest: Y-Y. Zhao is the founder and chief scientific officer of MountView Therapeutics LLC. This project utilises technologies subject to the following pending patents entitled “PLGA-PEG nanoparticles and methods of uses” and “Cationic polymer-formulated nanoparticles and methods of use” to Y-Y. Zhao. The other authors declare no conflicts of interest.
Références
J Appl Physiol (1985). 2001 Apr;90(4):1299-306
pubmed: 11247927
Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620-4
pubmed: 2154753
Sci Transl Med. 2013 Oct 23;5(208):208sr5
pubmed: 24154604
Am J Respir Crit Care Med. 2012 Aug 1;186(3):261-72
pubmed: 22679007
J Exp Med. 2007 Oct 1;204(10):2373-82
pubmed: 17893196
Sci Rep. 2021 Jul 21;11(1):14869
pubmed: 34290305
Trends Cardiovasc Med. 2017 May;27(4):229-236
pubmed: 28089339
Circulation. 2016 Jun 14;133(24):2447-58
pubmed: 27143681
J Biol Chem. 2014 Mar 14;289(11):7948-61
pubmed: 24469460
Eur Respir J. 2009 Jul;34(1):276
pubmed: 19567609
Circulation. 2009 Apr 28;119(16):2250-94
pubmed: 19332472
Circulation. 2004 Sep 14;110(11):1499-506
pubmed: 15353500
Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1191-1202
pubmed: 30943774
Pulm Pharmacol Ther. 2008;21(3):507-15
pubmed: 18226570
Antioxid Redox Signal. 2013 May 10;18(14):1723-6
pubmed: 23330936
Am J Respir Crit Care Med. 2018 Sep 15;198(6):788-802
pubmed: 29664678
J Clin Invest. 2009 Jul;119(7):2009-18
pubmed: 19487814
J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D42-50
pubmed: 24355641
Oncol Lett. 2018 Oct;16(4):4847-4854
pubmed: 30250550
Antioxid Redox Signal. 2013 May 10;18(14):1810-7
pubmed: 22870869
Am J Respir Crit Care Med. 2014 Feb 15;189(4):394-400
pubmed: 24401129
Oncol Rep. 2012 Mar;27(3):842-8
pubmed: 22024718
Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37
pubmed: 8944624
Am J Respir Crit Care Med. 2004 Mar 15;169(6):764-9
pubmed: 14701708
Trends Cardiovasc Med. 2009 Oct;19(7):238-42
pubmed: 20382348
Circ Cardiovasc Genet. 2012 Jun;5(3):336-43
pubmed: 22474227
Cell Rep. 2022 Jan 4;38(1):110196
pubmed: 34986352
Adv Exp Med Biol. 2017;967:33-45
pubmed: 29047079
Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):204-9
pubmed: 15615855
Am J Respir Crit Care Med. 2018 Dec 1;198(11):1423-1434
pubmed: 29924941
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11375-80
pubmed: 12177436
Chest. 2006 Mar;129(3):696-705
pubmed: 16537870
J Am Coll Cardiol. 2015 May 12;65(18):1976-97
pubmed: 25953750
Int J Mol Sci. 2021 Mar 20;22(6):
pubmed: 33804745
J Physiol. 2006 Dec 1;577(Pt 2):705-16
pubmed: 16973705
Clin Transl Sci. 2008 Sep;1(2):99-106
pubmed: 20443830
Circulation. 2019 Feb 12;139(7):932-948
pubmed: 30586714
Antioxidants (Basel). 2017 Jul 06;6(3):
pubmed: 28684719
Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L233-45
pubmed: 18083771
Am J Pathol. 2012 Jun;180(6):2268-75
pubmed: 22632818