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Open Access Green as soon as Postprint is submitted to ZB.
Methylglyoxal drives a distinct, nonclassical macrophage activation status.
Thromb. Haemost. 121, 1464-1475 (2021)
Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Methylglyoxal ; Macrophage Polarization ; Diabetes ; Metabolic Activation
ISSN (print) / ISBN
0340-6245
Journal
Thrombosis and Haemostasis
Quellenangaben
Volume: 121,
Issue: 11,
Pages: 1464-1475
Publisher
Schattauer
Publishing Place
Rudigerstr 14, D-70469 Stuttgart, Germany
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
Grants
Deutsches Zentrum fur Herz-Kreislauf-Forschung Junior Research Group grant
Deutsche Forschungsgemeinschaft
Helmholtz Future Topic AMPro
Collaborative Research Center "Reactive metabolites and diabetic complications"
Deutsche Forschungsgemeinschaft
Helmholtz Future Topic AMPro
Collaborative Research Center "Reactive metabolites and diabetic complications"