CROT (Carnitine O-Octanoyltransferase) Is a Novel Contributing Factor in Vascular Calcification via Promoting Fatty Acid Metabolism and Mitochondrial Dysfunction.
Adult
Animals
Atherosclerosis
/ enzymology
Carnitine Acyltransferases
/ genetics
Cells, Cultured
Disease Models, Animal
Energy Metabolism
Fatty Acids
/ metabolism
Female
Fibrosis
Humans
Male
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Mitochondria
/ enzymology
Muscle, Smooth, Vascular
/ enzymology
Myocytes, Smooth Muscle
/ enzymology
Osteogenesis
Proteome
Proteomics
Receptors, LDL
/ genetics
Signal Transduction
Vascular Calcification
/ enzymology
cholesterol
lipidomics
mitochondria
muscle cells
proteomics
Journal
Arteriosclerosis, thrombosis, and vascular biology
ISSN: 1524-4636
Titre abrégé: Arterioscler Thromb Vasc Biol
Pays: United States
ID NLM: 9505803
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
pubmed:
29
12
2020
medline:
2
6
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
Vascular calcification is a critical pathology associated with increased cardiovascular event risk, but there are no Food and Drug Administration-approved anticalcific therapies. We hypothesized and validated that an unbiased screening approach would identify novel mediators of human vascular calcification. Approach and Results: We performed an unbiased quantitative proteomics and pathway network analysis that identified increased CROT (carnitine O-octanoyltransferase) in calcifying primary human coronary artery smooth muscle cells (SMCs). Additionally, human carotid artery atherosclerotic plaques contained increased immunoreactive CROT near calcified regions. CROT is a novel contributing factor in vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction, as such CROT inhibition has strong potential as an antifibrocalcific therapy.
Identifiants
pubmed: 33356393
doi: 10.1161/ATVBAHA.120.315007
pmc: PMC8105275
mid: NIHMS1654798
doi:
Substances chimiques
Fatty Acids
0
Proteome
0
Receptors, LDL
0
Carnitine Acyltransferases
EC 2.3.1.-
carnitine octanoyltransferase
EC 2.3.1.-
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
Pagination
755-768Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL136431
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141917
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147095
Pays : United States
Références
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9232-7
pubmed: 21576456
Circulation. 2007 Jan 23;115(3):377-86
pubmed: 17224478
Atherosclerosis. 2011 Mar;215(1):43-51
pubmed: 21193197
Trends Endocrinol Metab. 2014 Sep;25(9):481-7
pubmed: 25034130
J Biol Chem. 2005 Jan 7;280(1):738-44
pubmed: 15492013
Circ Res. 2006 Mar 31;98(6):727-9
pubmed: 16514067
Kidney Int. 2004 Dec;66(6):2293-9
pubmed: 15569318
Exp Mol Pathol. 1985 Apr;42(2):139-62
pubmed: 3884359
J Vasc Surg. 2007 Jun;45 Suppl A:A25-32
pubmed: 17544021
Nat Rev Cardiol. 2019 May;16(5):261-274
pubmed: 30531869
Nature. 2014 Jun 5;510(7503):92-101
pubmed: 24899309
Heart. 2014 Apr;100(7):569-73
pubmed: 24352736
Nat Mater. 2016 Mar;15(3):335-43
pubmed: 26752654
Eur J Clin Nutr. 2020 Apr;74(4):651-656
pubmed: 31896827
Biochem Biophys Res Commun. 2011 Jun 17;409(4):699-704
pubmed: 21619872
JAMA. 2004 Jan 14;291(2):210-5
pubmed: 14722147
J Clin Invest. 2016 Apr 1;126(4):1323-36
pubmed: 26950419
Circ Genom Precis Med. 2020 Jun;13(3):e002710
pubmed: 32397743
Semin Immunopathol. 2019 Nov;41(6):757-766
pubmed: 31696250
Prostaglandins Leukot Essent Fatty Acids. 1998 Sep;59(3):221-7
pubmed: 9844996
Nutrients. 2017 Aug 10;9(8):
pubmed: 28796175
Int Rev Cell Mol Biol. 2011;288:43-99
pubmed: 21482410
Circulation. 2006 Oct 17;114(16):1761-91
pubmed: 17015792
Circulation. 2020 May 26;141(21):1670-1680
pubmed: 32223336
Arterioscler Thromb Vasc Biol. 2020 Mar;40(3):656-669
pubmed: 31852220
Sci Adv. 2020 Sep 16;6(38):
pubmed: 32938681
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Circ Res. 2013 Jun 21;113(1):72-7
pubmed: 23616621
Circ Res. 2017 Jul 21;121(3):220-233
pubmed: 28607103
Nat Rev Cardiol. 2019 Dec;16(12):727-744
pubmed: 31243391
PLoS One. 2017 Aug 3;12(8):e0181009
pubmed: 28771600
Mol Genet Metab. 2000 Sep-Oct;71(1-2):139-53
pubmed: 11001805
Front Cardiovasc Med. 2019 Apr 16;6:49
pubmed: 31041314
Arterioscler Thromb Vasc Biol. 2020 Jul;40(7):e214-e226
pubmed: 32493171
J Biol Chem. 1984 Nov 10;259(21):13089-95
pubmed: 6436243
Mol Metab. 2018 Sep;15:45-55
pubmed: 29858147
Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10741-6
pubmed: 23733926
J Proteome Res. 2019 Feb 1;18(2):775-781
pubmed: 30370770
Biochem Biophys Res Commun. 1999 Sep 16;263(1):213-8
pubmed: 10486279