Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis
Mehra VC, Jackson E, Zhang XM, Jiang XC, Dobrucki LW, Yu J, Bernatchez P, Sinusas AJ, Shulman GI, Sessa WC, Yarovinsky TO, Bender JR. Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis. American Journal Of Pathology 2014, 184: 1562-1576. PMID: 24606881, PMCID: PMC4005977, DOI: 10.1016/j.ajpath.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaArteriesCattleCeramidesDiet, High-FatEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHaploinsufficiencyHindlimbHumansIschemiaMice, Inbred C57BLNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPalmitic AcidPhosphorylationProtein Phosphatase 2Proto-Oncogene Proteins c-aktSerine C-PalmitoyltransferaseSignal TransductionVascular Endothelial Growth Factor AConceptsPP2A inhibitor okadaic acidProtein phosphatase 2AInhibitor okadaic acidVEGF-induced signalingSerine palmitoyltransferase inhibitor myriocinDe novo ceramide synthesisPhosphatase 2AENOS agonistsNovo ceramide synthesisPalmitic acidAngiogenic responsePotential molecular targetsOkadaic acidEndothelial cellsEarly speciesEndothelial cell responsesCord formationVEGFR2 phosphorylationSaturated free fatty acidVEGF resistanceCeramide synthesisResistance mechanismsMolecular targetsVascular homeostasisPhosphorylation