TY  - JOUR
A1  - Fißlthaler, Beate
A1  - Zippel, Nina
A1  - Abdel Malik, Randa
A1  - Delgado Lagos, Fredy
A1  - Zukunft, Sven
A1  - Thoele, Janina
A1  - Siuda, Daniel
A1  - Söhnlein, Oliver
A1  - Wittig, Ilka
A1  - Heidler, Juliana
A1  - Weigert, Andreas
A1  - Fleming, Ingrid
T1  - Myeloid-specific deletion of the AMPK2 subunit alters monocyte protein expression and atherogenesis
T2  - International journal of molecular sciences
N2  - 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.
KW  - DNA methylation
KW  - matrix metalloproteinase
KW  - macrophage
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51069
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-510697
SN  - 1422-0067
SN  - 1661-6596
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
VL  - 20
IS  - 12, Art. 3005
SP  - 1
EP  - 17
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -