TY  - JOUR
A1  - Hitzel, Juliane
A1  - Lee, Eunjee
A1  - Zhang, Yi
A1  - Bibli, Sofia Iris
A1  - Li, Xiaogang
A1  - Zukunft, Sven
A1  - Pflüger, Beatrice
A1  - Hu, Jiong
A1  - Schürmann, Christoph
A1  - Vasconez, Andrea Estefania
A1  - Oo, James A.
A1  - Kratzer, Adelheid
A1  - Kumar, Sandeep
A1  - Rezende Felipe, Flávia Figueiredo de
A1  - Josipovic, Ivana
A1  - Thomas, Dominique Jeanette
A1  - Giral, Hector
A1  - Schreiber, Yannick
A1  - Geisslinger, Gerd
A1  - Fork, Christian
A1  - Yang, Xia
A1  - Sigala, Fragiska
A1  - Romanoski, Casey E.
A1  - Kroll, Jens
A1  - Jo, Hanjoong
A1  - Landmesser, Ulf
A1  - Lusis, Aldons J.
A1  - Namgaladze, Dmitry
A1  - Fleming, Ingrid
A1  - Leisegang, Matthias
A1  - Zhu, Jianhui
A1  - Brandes, Ralf
T1  - Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells
T2  - Nature Communications
N2  - Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a causal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipoproteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2-controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis.
KW  - Atherosclerosis
KW  - Bayesian inference
KW  - Phospholipids
KW  - Regulatory networks
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46692
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-466925
SN  - 2041-1723
N1  - Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 9
IS  - 1, Art. 2292
SP  - 1
EP  - 18
PB  - Nature Publishing Group UK
CY  - [London]
ER  -