Myeloid-Specific Deletion of the AMPKa2 Subunit Alters Monocyte Protein Expression and Atherogenesis
Beate Fisslthaler, Nina Zippel, Randa Abdel Malik, Fredy Delgado Lagos, Sven Zukunft, Janina Thoele, Daniele Suida, Oliver Soehnlein, Ilka Wittig, Juliana Heidler, Andreas Weigert, Ingrid Fleming| Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60596 Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Partner site RhineMain, 60596 Frankfurt am Main, Germany; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, 80336 Munich, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80336 Munich, Germany; Department of Physiology and Pharmacology and Department of Medicine, Karolinska Institute, 17177 Stockholm, Sweden; Functional Proteomics, SFB 815 Core Unit, Goethe University, 60596 Frankfurt am Main, Germany; Institute of Biochemistry I, Goethe-University Frankfurt, 60596 Frankfurt am Main, Germany|2019|Internal Journal of Molecular Science|20,3005 doi:10.3390/ijms20123005
AMP-activated protein kinase (AMPK) is an energy kinase that is activated by a drop in cellular ATP levels. AMPK also have an important role in regulating vascular function, where specific downregulation of AMPKa2 has clear effects on cell function. There is currently very little known about the role of AMPKa2 subunits in the regulation of myeloid cell function. The AMPKa2 subunit was reported to play a determinant role in neutrophil survival in hypoxic conditions in ischemic hindlimbs. Thereby contributing to the process of arteriogenesis/angiogenesis. The aim of the study was to assess the consequences of myeloid-specific AMPKa2 deletion on protein expression in monocytes/macrophages and atherogenesis. For the analysis, total RNA and DNA was extracted, gene expression and DNA methylation quantification were performed by RT-qPCR and qPCR on the Mic qPCR cycler. All samples were normalized to their corresponding input and wild-type animals. A proteomics approach was also applied to bone marrow derived monocytes from wild-type mice vs mice containing the AMPKa2 deletion in myeloid cells. It was found that AMPKa2 subunit in myeloid cells influenced protein expression and DNA methylation by increasing the ratio of S-adenosyl methionine to S-adenosyl homocysteine. As a result, AMPKa2 subunit contributes to atherosclerotic plaque formation.