Transcriptome-based identification of new anti-anti-inflammatory and vasodilating properties of the n-3 fatty acid docosahexaenoic acid in vascular endothelial cell under proinflammatory conditions
Autor: | Rosanna Martinelli, Marika Massaro, Carlo Storelli, Liborio Stuppia, Raffaele De Caterina, Valentina Gatta, Nadia Calabriso, Tonia Buonomo, Maria Annunziata Carluccio, Egeria Scoditti, Mariangela Pellegrino |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Genetics and Molecular Biology (all)
Endothelium Endothelial cells lcsh:Medicine Microarray Pharmacology Biology Biochemistry Proinflammatory cytokine Transcriptome Agricultural and Biological Sciences (all) Medicine (all) DNA-binding proteins Gene expression medicine Gene regulation Genetic interference Small interfering RNAs lcsh:Science Regulation of gene expression chemistry.chemical_classification Multidisciplinary lcsh:R Fatty acid 3. Good health Gene expression profiling medicine.anatomical_structure chemistry Docosahexaenoic acid Immunology lcsh:Q Research Article |
Zdroj: | PLoS ONE, Vol 10, Iss 6, p e0129652 (2015) PLoS ONE |
Popis: | Scope 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. Methods and 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. |
Databáze: | OpenAIRE |
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