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Article

Myeloid-Specific Deletion of the AMPKα2 Subunit Alters Monocyte Protein Expression and Atherogenesis

1
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60596 Frankfurt am Main, Germany
2
German Center of Cardiovascular Research (DZHK), Partner site RhineMain, 60596 Frankfurt am Main, Germany
3
Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, 80336 Munich, Germany
4
German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80336 Munich, Germany
5
Department of Physiology and Pharmacology and Department of Medicine, Karolinska Institute, 17177 Stockholm, Sweden
6
Functional Proteomics, SFB 815 Core Unit, Goethe University, 60596 Frankfurt am Main, Germany
7
Institute of Biochemistry I, Goethe-University Frankfurt, 60596 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(12), 3005; https://doi.org/10.3390/ijms20123005
Received: 6 May 2019 / Revised: 16 June 2019 / Accepted: 17 June 2019 / Published: 19 June 2019
(This article belongs to the Special Issue Kinase Signal Transduction 2019)
The AMP-activated protein kinase (AMPK) is an energy sensing kinase that is activated by a drop in cellular ATP levels. Although several studies have addressed the role of the AMPKα1 subunit in monocytes and macrophages, little is known about the α2 subunit. The aim of this study was to assess the consequences of AMPKα2 deletion on protein expression in monocytes/macrophages, as well as on atherogenesis. A proteomics approach was applied to bone marrow derived monocytes from wild-type mice versus mice specifically lacking AMPKα2 in myeloid cells (AMPKα2∆MC mice). This revealed differentially expressed proteins, including methyltransferases. Indeed, AMPKα2 deletion in macrophages increased the ratio of S-adenosyl methionine to S-adenosyl homocysteine and increased global DNA cytosine methylation. Also, methylation of the vascular endothelial growth factor and matrix metalloproteinase-9 (MMP9) genes was increased in macrophages from AMPKα2∆MC mice, and correlated with their decreased expression. To link these findings with an in vivo phenotype, AMPKα2∆MC mice were crossed onto the ApoE-/- background and fed a western diet. ApoExAMPKα2∆MC mice developed smaller atherosclerotic plaques than their ApoExα2fl/fl littermates, that contained fewer macrophages and less MMP9 than plaques from ApoExα2fl/fl littermates. These results indicate that the AMPKα2 subunit in myeloid cells influences DNA methylation and thus protein expression and contributes to the development of atherosclerotic plaques. View Full-Text
Keywords: DNA methylation; matrix metalloproteinase; macrophage DNA methylation; matrix metalloproteinase; macrophage
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MDPI and ACS Style

Fisslthaler, B.; Zippel, N.; Abdel Malik, R.; Delgado Lagos, F.; Zukunft, S.; Thoele, J.; Siuda, D.; Soehnlein, O.; Wittig, I.; Heidler, J.; Weigert, A.; Fleming, I. Myeloid-Specific Deletion of the AMPKα2 Subunit Alters Monocyte Protein Expression and Atherogenesis. Int. J. Mol. Sci. 2019, 20, 3005. https://doi.org/10.3390/ijms20123005

AMA Style

Fisslthaler B, Zippel N, Abdel Malik R, Delgado Lagos F, Zukunft S, Thoele J, Siuda D, Soehnlein O, Wittig I, Heidler J, Weigert A, Fleming I. Myeloid-Specific Deletion of the AMPKα2 Subunit Alters Monocyte Protein Expression and Atherogenesis. International Journal of Molecular Sciences. 2019; 20(12):3005. https://doi.org/10.3390/ijms20123005

Chicago/Turabian Style

Fisslthaler, Beate; Zippel, Nina; Abdel Malik, Randa; Delgado Lagos, Fredy; Zukunft, Sven; Thoele, Janina; Siuda, Daniel; Soehnlein, Oliver; Wittig, Ilka; Heidler, Juliana; Weigert, Andreas; Fleming, Ingrid. 2019. "Myeloid-Specific Deletion of the AMPKα2 Subunit Alters Monocyte Protein Expression and Atherogenesis" Int. J. Mol. Sci. 20, no. 12: 3005. https://doi.org/10.3390/ijms20123005

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