Partial Inhibition of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase-3 (PFKFB3) Enzyme in Myeloid Cells Does Not Affect Atherosclerosis.

PFKFB3 atherosclerosis dendritic cell glycolysis glycolysis inhibition macrophage myeloid cells neutrophil

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2021
Historique:
received: 15 04 2021
accepted: 26 07 2021
entrez: 30 8 2021
pubmed: 31 8 2021
medline: 31 8 2021
Statut: epublish

Résumé

The protein 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a key stimulator of glycolytic flux. Systemic, partial PFKFB3 inhibition previously decreased total plaque burden and increased plaque stability. However, it is unclear which cell type conferred these positive effects. Myeloid cells play an important role in atherogenesis, and mainly rely on glycolysis for energy supply. Thus, we studied whether myeloid inhibition of PFKFB3-mediated glycolysis in Analysis of atherosclerotic human and murine single-cell populations confirmed Partial myeloid knockdown of PFKFB3 did not affect atherosclerosis development in advanced or early lesions. Previously reported positive effects of systemic, partial PFKFB3 inhibition on lesion stabilization, do not seem conferred by monocytes, macrophages or neutrophils. Instead, other

Sections du résumé

BACKGROUND BACKGROUND
The protein 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a key stimulator of glycolytic flux. Systemic, partial PFKFB3 inhibition previously decreased total plaque burden and increased plaque stability. However, it is unclear which cell type conferred these positive effects. Myeloid cells play an important role in atherogenesis, and mainly rely on glycolysis for energy supply. Thus, we studied whether myeloid inhibition of PFKFB3-mediated glycolysis in
METHODS AND RESULTS RESULTS
Analysis of atherosclerotic human and murine single-cell populations confirmed
CONCLUSION CONCLUSIONS
Partial myeloid knockdown of PFKFB3 did not affect atherosclerosis development in advanced or early lesions. Previously reported positive effects of systemic, partial PFKFB3 inhibition on lesion stabilization, do not seem conferred by monocytes, macrophages or neutrophils. Instead, other

Identifiants

pubmed: 34458258
doi: 10.3389/fcell.2021.695684
pmc: PMC8387953
doi:

Types de publication

Journal Article

Langues

eng

Pagination

695684

Informations de copyright

Copyright © 2021 Tillie, De Bruijn, Perales-Patón, Temmerman, Ghosheh, Van Kuijk, Gijbels, Carmeliet, Ley, Saez-Rodriguez and Sluimer.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Front Immunol. 2014 Sep 02;5:420
pubmed: 25228902
Cold Spring Harb Symp Quant Biol. 2011;76:211-6
pubmed: 22096029
Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):12-22
pubmed: 14604830
Sci Rep. 2019 Dec 30;9(1):20333
pubmed: 31889092
Front Immunol. 2019 Sep 20;10:2099
pubmed: 31616403
Circ Res. 2020 Jul 17;127(3):402-426
pubmed: 32673538
Cell. 2011 Apr 29;145(3):341-55
pubmed: 21529710
Circ Res. 2020 Apr 24;126(9):1297-1319
pubmed: 32324497
J Leukoc Biol. 2011 Apr;89(4):557-63
pubmed: 21248152
Front Immunol. 2019 Apr 25;10:775
pubmed: 31073300
Nat Med. 2019 Aug;25(8):1280-1289
pubmed: 31359001
Cell. 2013 Aug 1;154(3):651-63
pubmed: 23911327
ACS Nano. 2019 Dec 24;13(12):13759-13774
pubmed: 31268670
Nat Rev Cardiol. 2020 Jun;17(6):327-340
pubmed: 31996800
Annu Rev Cell Dev Biol. 2011;27:441-64
pubmed: 21985671
Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):242-9
pubmed: 16373607
Nat Rev Immunol. 2019 Feb;19(2):89-103
pubmed: 30464294
Curr Opin Lipidol. 2018 Dec;29(6):474-480
pubmed: 30234554
Sci Rep. 2019 Aug 30;9(1):12608
pubmed: 31471554
J Med Chem. 2015 Apr 23;58(8):3611-25
pubmed: 25849762
Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1419-23
pubmed: 19696407
Semin Immunopathol. 2014 Jan;36(1):93-102
pubmed: 24196454
Genome Res. 2019 Aug;29(8):1363-1375
pubmed: 31340985
FEBS Lett. 2020 Sep;594(18):3067-3075
pubmed: 32620030
Arterioscler Thromb Vasc Biol. 2020 May;40(5):1168-1181
pubmed: 32188275
Cell. 2007 Feb 9;128(3):425-30
pubmed: 17289560
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Circulation. 2007 Oct 16;116(16):1832-44
pubmed: 17938300
Arterioscler Thromb Vasc Biol. 2015 Apr;35(4):763-70
pubmed: 25675999
Clin Exp Immunol. 2021 Jun 10;:
pubmed: 34109619
Cardiovasc Res. 2021 Apr 26;:
pubmed: 33913468
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Cell Metab. 2014 Jan 7;19(1):37-48
pubmed: 24332967
Transgenic Res. 1999 Aug;8(4):265-77
pubmed: 10621974
Front Cell Dev Biol. 2020 Nov 12;8:581641
pubmed: 33282864
Circ Res. 2015 Mar 27;116(7):1231-44
pubmed: 25814684
Sci Rep. 2019 Aug 12;9(1):11670
pubmed: 31406177
J Pathol. 2020 Apr;250(5):705-714
pubmed: 32003464
Blood. 2000 Jul 15;96(2):719-26
pubmed: 10887140
Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1463-71
pubmed: 25882065
Genome Biol. 2020 Feb 12;21(1):36
pubmed: 32051003

Auteurs

Renée J H A Tillie (RJHA)

Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands.

Jenny De Bruijn (J)

Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands.

Javier Perales-Patón (J)

Faculty of Medicine, Institute for Computational Biomedicine, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
Institute of Experimental Medicine and Systems Biology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany.

Lieve Temmerman (L)

Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands.

Yanal Ghosheh (Y)

La Jolla Institute for Immunology, San Diego, CA, United States.

Kim Van Kuijk (K)

Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands.

Marion J Gijbels (MJ)

Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands.
Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands.
Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

Peter Carmeliet (P)

Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
State Key Laboratory of Ophthalmology, Zhongshan Opthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Klaus Ley (K)

La Jolla Institute for Immunology, San Diego, CA, United States.
Department of Bioengineering, University of California, San Diego, San Diego, CA, United States.

Julio Saez-Rodriguez (J)

Faculty of Medicine, Institute for Computational Biomedicine, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
Institute of Experimental Medicine and Systems Biology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany.

Judith C Sluimer (JC)

Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands.
British Heart Foundation (BHF) Centre for Cardiovascular Sciences (CVS), University of Edinburgh, Edinburgh, United Kingdom.

Classifications MeSH