| First Author | Fisslthaler B | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 20 |
| Issue | 12 | PubMed ID | 31248224 |
| Mgi Jnum | J:289318 | Mgi Id | MGI:6434990 |
| Doi | 10.3390/ijms20123005 | Citation | Fisslthaler B, et al. (2019) Myeloid-Specific Deletion of the AMPKalpha2 Subunit Alters Monocyte Protein Expression and Atherogenesis. Int J Mol Sci 20(12):3005 |
| abstractText | 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 AMPKalpha1 subunit in monocytes and macrophages, little is known about the alpha2 subunit. The aim of this study was to assess the consequences of AMPKalpha2 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 AMPKalpha2 in myeloid cells (AMPKalpha2(MC) mice). This revealed differentially expressed proteins, including methyltransferases. Indeed, AMPKalpha2 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 AMPKalpha2(MC) mice, and correlated with their decreased expression. To link these findings with an in vivo phenotype, AMPKalpha2(MC) mice were crossed onto the ApoE(-/-) background and fed a western diet. ApoExAMPKalpha2(MC) mice developed smaller atherosclerotic plaques than their ApoExalpha2(fl/fl) littermates, that contained fewer macrophages and less MMP9 than plaques from ApoExalpha2(fl/fl) littermates. These results indicate that the AMPKalpha2 subunit in myeloid cells influences DNA methylation and thus protein expression and contributes to the development of atherosclerotic plaques. |
