TY - JOUR
TI - Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to
facilitate nucleotide release in endothelial cells
AU - Hitzel, Juliane
AU - Lee, Eunjee
AU - Zhang, Yi
AU - Bibli, Sofia Iris and
AU - Li, Xiaogang
AU - Zukunft, Sven
AU - Pflueger, Beatrice
AU - Hu, Jiong and
AU - Schuermann, Christoph
AU - Vasconez, Andrea Estefania
AU - Oo, James A.
AU - and Kratzer, Adelheid
AU - Kumar, Sandeep
AU - Rezende, Flavia and
AU - Josipovic, Ivana
AU - Thomas, Dominique
AU - Giral, Hector
AU - Schreiber,
AU - Yannick
AU - Geisslinger, Gerd
AU - Fork, Christian
AU - Yang, Xia and
AU - Sigala, Fragiska
AU - Romanoski, Casey E.
AU - Kroll, Jens
AU - Jo,
AU - Hanjoong
AU - Landmesser, Ulf
AU - Lusis, Aldons J.
AU - Namgaladze, Dmitry
AU - and Fleming, Ingrid
AU - Leisegang, Matthias S.
AU - Zhu, Jun
AU - Brandes,
AU - Ralf P.
JO - Nature Communications
PY - 2018
VL - 9
TODO - null
SP - null
PB - Nature Publishing Group
SN - 2041-1723
TODO - 10.1038/s41467-018-04602-0
TODO - null
TODO - 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.
ER -