@article{3180390,
    title = "Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to
facilitate nucleotide release in endothelial cells",
    author = "Hitzel, Juliane and Lee, Eunjee and Zhang, Yi and Bibli, Sofia Iris and and Li, Xiaogang and Zukunft, Sven and Pflueger, Beatrice and Hu, Jiong and and Schuermann, Christoph and Vasconez, Andrea Estefania and Oo, James A. and and Kratzer, Adelheid and Kumar, Sandeep and Rezende, Flavia and and Josipovic, Ivana and Thomas, Dominique and Giral, Hector and Schreiber, and Yannick and Geisslinger, Gerd and Fork, Christian and Yang, Xia and and Sigala, Fragiska and Romanoski, Casey E. and Kroll, Jens and Jo, and Hanjoong and Landmesser, Ulf and Lusis, Aldons J. and Namgaladze, Dmitry and and Fleming, Ingrid and Leisegang, Matthias S. and Zhu, Jun and Brandes, and Ralf P.",
    journal = "Nature Communications",
    year = "2018",
    volume = "9",
    publisher = "Nature Publishing Group",
    issn = "2041-1723",
    doi = "10.1038/s41467-018-04602-0",
    abstract = "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."
}