title: Transcriptome-based identification of new anti-inflammatory and vasodilating properties of the n-3 fatty acid docosahexaenoic acid in vascular endothelial cell under proinflammatory conditions [corrected].
abstract: METHODS
  High intakes of n-3 fatty acids exert anti-inflammatory effects and cardiovascular protection, but the underlying molecular basis is incompletely defined. By genome-wide analysis we searched for novel effects of docosahexaenoic acid (DHA) on gene expression and pathways in human vascular endothelium under pro-inflammatory conditions.
  
  
  RESULTS
  Human umbilical vein endothelial cells were treated with DHA and then stimulated with interleukin(IL)-1β. Total RNA was extracted, and gene expression examined by DNA microarray. DHA alone altered the expression of 188 genes, decreasing 92 and increasing 96. IL-1β changed the expression of 2031 genes, decreasing 997 and increasing 1034. Treatment with DHA before stimulation significantly affected the expression of 116 IL-1β-deregulated genes, counter-regulating the expression of 55 genes among those decreased and of 61 among those increased. Functional and network analyses identified immunological, inflammatory and metabolic pathways as the most affected. Newly identified DHA-regulated genes are involved in stemness, cellular growth, cardiovascular system function and cancer, and included cytochrome p450 4F2(CYP4F2), transforming growth factor(TGF)-β2, Cluster of Differentiation (CD)47, caspase recruitment domain(CARD)11 and phosphodiesterase(PDE)5α.
  
  
  CONCLUSIONS
  Endothelial exposure to DHA regulates novel genes and related pathways. Such unbiased identification should increase our understanding of mechanisms by which n-3 fatty acids affect human diseases.
authors.affiliation: National Research Council (CNR), Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Massaro
authors.affiliation: CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Medicine and Surgery of Salerno University, Salerno, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Martinelli
authors.affiliation: "Gabriele d'Annunzio" University and Center of Excellence on Aging, Chieti, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gatta
authors.affiliation: National Research Council (CNR), Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Egeria
authors.initials: E
authors.lastname: Scoditti
authors.affiliation: National Research Council (CNR), Institute of Clinical Physiology, Lecce, Italy; Department of Biological and Environmental Science and Technology (Disteba), University of Salento, Lecce, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pellegrino
authors.affiliation: National Research Council (CNR), Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Maria Annunziata
authors.initials: MA
authors.lastname: Carluccio
authors.affiliation: National Research Council (CNR), Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Calabriso
authors.affiliation: CEINGE Biotecnologie Avanzate, Naples, Italy.
authors.forename: Tonia
authors.initials: T
authors.lastname: Buonomo
authors.affiliation: "Gabriele d'Annunzio" University and Center of Excellence on Aging, Chieti, Italy.
authors.forename: Liborio
authors.initials: L
authors.lastname: Stuppia
authors.affiliation: Department of Biological and Environmental Science and Technology (Disteba), University of Salento, Lecce, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Storelli
authors.affiliation: "Gabriele d'Annunzio" University and Center of Excellence on Aging, Chieti, Italy; Fondazione Toscana "Gabriele Monasterio", Pisa, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D053468:CARD Signaling Adaptor Proteins; D051928:CD47 Antigen; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014665:Vasodilator Agents; D004281:Docosahexaenoic Acids; C426242:CARD11 protein, human; D006162:Guanylate Cyclase