Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques.
coronary artery disease
gene expression
lipids
plaque
women's health
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:
10 2023
10 2023
Historique:
medline:
4
10
2023
pubmed:
17
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male Here, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene Female atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs.
Sections du résumé
BACKGROUND
Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown.
METHODS
Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male
RESULTS
Here, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene
CONCLUSIONS
Female atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs.
Identifiants
pubmed: 37589136
doi: 10.1161/ATVBAHA.123.319325
pmc: PMC10521798
mid: NIHMS1922286
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1836-1850Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL136314
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141425
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL156849
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL166161
Pays : United States
Commentaires et corrections
Type : UpdateOf
Références
Atherosclerosis. 2020 Oct;310:1-10
pubmed: 32861960
Circ Res. 2016 Feb 19;118(4):692-702
pubmed: 26892967
Nature. 2001 May 3;411(6833):41-2
pubmed: 11333967
Atherosclerosis. 2015 Mar;239(1):260-7
pubmed: 25634157
Cardiovasc Res. 2018 Mar 15;114(4):540-550
pubmed: 29385543
JAMA. 2021 Mar 16;325(11):1043-1044
pubmed: 33616637
JCI Insight. 2020 Aug 6;5(15):
pubmed: 32634125
Circulation. 2020 Nov 24;142(21):2045-2059
pubmed: 32674599
Nat Rev Cardiol. 2009 Nov;6(11):681-8
pubmed: 19786983
Cell Rep. 2012 Sep 27;2(3):666-73
pubmed: 22939981
Circulation. 2021 Feb 16;143(7):713-726
pubmed: 33499648
Commun Biol. 2022 Aug 17;5(1):802
pubmed: 35978133
Nat Commun. 2018 Nov 22;9(1):4934
pubmed: 30467383
Cardiovasc Res. 2018 Jul 15;114(9):1241-1257
pubmed: 29617720
Nat Med. 2019 Aug;25(8):1280-1289
pubmed: 31359001
Atherosclerosis. 2015 Apr;239(2):528-38
pubmed: 25721704
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
Nat Rev Genet. 2011 Jan;12(1):56-68
pubmed: 21164525
Cardiovasc Res. 2019 Feb 1;115(2):453-462
pubmed: 30052805
Circulation. 2020 Nov 24;142(21):2060-2075
pubmed: 32962412
Arterioscler Thromb Vasc Biol. 2021 Nov;41(11):2693-2707
pubmed: 34470477
Amyloid. 2006 Jun;13(2):78-85
pubmed: 16911961
Genome Biol. 2014;15(12):550
pubmed: 25516281
Exp Mol Pathol. 2015 Dec;99(3):654-62
pubmed: 26551087
Curr Opin Lipidol. 2017 Oct;28(5):434-441
pubmed: 28682809
Nat Genet. 2017 Sep;49(9):1392-1397
pubmed: 28714974
Nat Genet. 1999 Feb;21(2):150-1
pubmed: 9988260
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17402-7
pubmed: 17090670
J Vasc Surg. 2007 Dec;46(6):1147-54
pubmed: 17950565
Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1500-5
pubmed: 10845864
J Vasc Surg. 2007 Feb;45(2):289-96; discussion 296-7
pubmed: 17264005
JAMA. 2012 Feb 22;307(8):813-22
pubmed: 22357832
Arch Intern Med. 1998 Oct 12;158(18):2054-62
pubmed: 9778206
Sci Rep. 2017 Jan 27;7:41483
pubmed: 28128285
Science. 2016 Aug 19;353(6301):827-30
pubmed: 27540175
J Am Heart Assoc. 2019 Nov 5;8(21):e012322
pubmed: 31640466
Am Heart J. 2001 Feb;141(2 Suppl):S58-62
pubmed: 11174360
N Engl J Med. 2020 Nov 5;383(19):1838-1847
pubmed: 32865380
Curr Opin Lipidol. 2014 Oct;25(5):374-9
pubmed: 25110900
N Engl J Med. 2017 Sep 21;377(12):1119-1131
pubmed: 28845751
Eur Heart J Open. 2021 Dec 21;2(1):oeab043
pubmed: 35174364
Nat Rev Genet. 2019 May;20(5):257-272
pubmed: 30696980
Nat Genet. 2022 Dec;54(12):1803-1815
pubmed: 36474045
Nat Genet. 2015 Oct;47(10):1121-1130
pubmed: 26343387
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Eur J Pharmacol. 2017 Dec 5;816:129-137
pubmed: 28899695
Eur J Epidemiol. 2004;19(12):1127-33
pubmed: 15678794
Nat Commun. 2019 Jun 14;10(1):2631
pubmed: 31201301
Breast. 2006 Apr;15(2):142-57
pubmed: 16289904
N Engl J Med. 1997 May 1;336(18):1276-82
pubmed: 9113930
J Am Coll Cardiol. 2018 Sep 4;72(10):1081-1090
pubmed: 30165978
Circ Res. 2020 Nov 6;127(11):1437-1455
pubmed: 32981416
Stat Appl Genet Mol Biol. 2005;4:Article17
pubmed: 16646834
J Am Coll Cardiol. 2010 Mar 16;55(11):1057-65
pubmed: 20223363
Nat Metab. 2021 Feb;3(2):166-181
pubmed: 33619382
BMC Bioinformatics. 2008 Dec 29;9:559
pubmed: 19114008
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Circulation. 1996 Apr 1;93(7):1354-63
pubmed: 8641024
Genome Biol. 2016 Apr 28;17:77
pubmed: 27121950
Arterioscler Thromb Vasc Biol. 2021 Apr;41(4):1408-1427
pubmed: 33626908
Arterioscler Thromb Vasc Biol. 2019 May;39(5):876-887
pubmed: 30786740