title: Palmitate and oleate have distinct effects on the inflammatory phenotype of human endothelial cells.
abstract: Free fatty acids may create a state of continuous and progressive damaging to the vascular wall manifested by endothelial dysfunction. In this study we determine the mechanisms by which fatty acids palmitate (C16:0) and oleate (C18:1) affect intracellular long chain acyl-CoA (LCAC) content, energy metabolism, cell survival and proliferation and activation of NF-kappaB in cultured endothelial cells. A 48-h exposure of human umbilical vein endothelial cells (HUVEC) to 0.5 mM palmitate or 0.5 mM oleate increased total long chain acyl-CoA (LCAC) content 1.7 and 2 fold, respectively and decreased ATP(total)/ADP(total) ratio by 26+/-5% (mean+/-SEM) and 15+/-2%, respectively, which was prevented by the acyl-CoA synthetase inhibitor triacsin C. Furthermore, palmitate inhibited cell proliferation by 34+/-5%, while oleate stimulated it by 12+/-2%. alpha-Tocopherol fully and triacsin C partially abolished the effect of palmitate on cell proliferation. Palmitate and oleate increased caspase-3 activity 3.2 and 1.4 fold, respectively. Palmitate-induced caspase-3 activation was prevented by triacsin C and slightly reduced by alpha-tocopherol and by the de novo ceramide synthesis inhibitor fumonisin B(1). Both fatty acids induced antioxidant-sensitive nuclear translocation of NF-kappaB after 72 h, but not after 48 h. In conclusion, we showed that fatty acids influence different aspects of HUVEC function resulting in amongst other activation of apoptotic and inflammatory pathways. Our results indicate that the effects depend on the fatty acid type and may be related to accumulation of LCAC.
authors.affiliation: Department of Molecular Cell Physiology, Institute for Molecular Cell Biology, VU University, Amsterdam, The Netherlands.
authors.forename: Jolita
authors.initials: J
authors.lastname: Ciapaite
authors.forename: Jan
authors.initials: J
authors.lastname: van Bezu
authors.forename: Gerco
authors.initials: G
authors.lastname: van Eikenhorst
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Klaas
authors.initials: K
authors.lastname: Krab
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D042783:Endothelial Cells / Q000187:drug effects*; D004734:Energy Metabolism; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D019308:Palmitic Acid / Q000494:pharmacology*
chemical_list: D000214:Acyl Coenzyme A; D016328:NF-kappa B; D019301:Oleic Acid; D019308:Palmitic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D053148:Caspase 3