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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.

Massaro M, Martinelli R, Gatta V, Scoditti E, Pellegrino M, Carluccio MA, Calabriso N, Buonomo T, Stuppia L, Storelli C, De Caterina R - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: National Research Council (CNR), Institute of Clinical Physiology, Lecce, Italy.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Top ten signaling and metabolic pathways regulated by interleukin (IL)-1β upon cell treatment with DHA.For the functional categorization of genes, Fischer’s exact test was used to calculate a P value (shown as bars), indicating the probability that each biological function assigned to the network is due to chance alone. The ratio (shown as squares) represents the number of differentially expressed genes in a given pathway divided by total number of genes making up that canonical pathway.
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pone.0129652.g003: Top ten signaling and metabolic pathways regulated by interleukin (IL)-1β upon cell treatment with DHA.For the functional categorization of genes, Fischer’s exact test was used to calculate a P value (shown as bars), indicating the probability that each biological function assigned to the network is due to chance alone. The ratio (shown as squares) represents the number of differentially expressed genes in a given pathway divided by total number of genes making up that canonical pathway.

Mentions: When classified by their function, these genes resulted associated with biological process including cancer, cell growth and proliferation, nervous system development and function, tissue development, and cardiovascular system development and function. Among such biological processes, most genes affected by DHA were related to breast and digestive system cancer (32 molecules), cell proliferation (28 molecules), and morphology of the cardiovascular system (10 molecules) (Table F in S2 File). IPA identified assorted canonical pathways associated with these genes. Ranked according to their significance (P value), they included: pigment epithelium-derived factor (PEDF) signaling, regulation of IL-2 expression in activated and anergic T lymphocytes, ultra-violet A (UVA)-induced MAPK signaling, interferon signaling, the role of tissue factor in cancer¸ proliferation-inducing ligand (APRIL)-mediated signaling, and p38 MAPK signaling (Fig 3). Genes included in each group of the top ten signaling pathway are listed in Table G in S2 File. When IPA was enquired for network analysis, it yielded 6 significant regulatory networks (score>2). The first ranked network (score = 38, focus molecules = 18) (S3 Fig) was associated with cellular function and maintenance, humoral immune response and protein synthesis. Top functions of the other 5 highly significant networks were associated with drug metabolism, cell death and survival, organ morphology and cardiovascular system development and function.


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.

Massaro M, Martinelli R, Gatta V, Scoditti E, Pellegrino M, Carluccio MA, Calabriso N, Buonomo T, Stuppia L, Storelli C, De Caterina R - PLoS ONE (2015)

Top ten signaling and metabolic pathways regulated by interleukin (IL)-1β upon cell treatment with DHA.For the functional categorization of genes, Fischer’s exact test was used to calculate a P value (shown as bars), indicating the probability that each biological function assigned to the network is due to chance alone. The ratio (shown as squares) represents the number of differentially expressed genes in a given pathway divided by total number of genes making up that canonical pathway.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482638&req=5

pone.0129652.g003: Top ten signaling and metabolic pathways regulated by interleukin (IL)-1β upon cell treatment with DHA.For the functional categorization of genes, Fischer’s exact test was used to calculate a P value (shown as bars), indicating the probability that each biological function assigned to the network is due to chance alone. The ratio (shown as squares) represents the number of differentially expressed genes in a given pathway divided by total number of genes making up that canonical pathway.
Mentions: When classified by their function, these genes resulted associated with biological process including cancer, cell growth and proliferation, nervous system development and function, tissue development, and cardiovascular system development and function. Among such biological processes, most genes affected by DHA were related to breast and digestive system cancer (32 molecules), cell proliferation (28 molecules), and morphology of the cardiovascular system (10 molecules) (Table F in S2 File). IPA identified assorted canonical pathways associated with these genes. Ranked according to their significance (P value), they included: pigment epithelium-derived factor (PEDF) signaling, regulation of IL-2 expression in activated and anergic T lymphocytes, ultra-violet A (UVA)-induced MAPK signaling, interferon signaling, the role of tissue factor in cancer¸ proliferation-inducing ligand (APRIL)-mediated signaling, and p38 MAPK signaling (Fig 3). Genes included in each group of the top ten signaling pathway are listed in Table G in S2 File. When IPA was enquired for network analysis, it yielded 6 significant regulatory networks (score>2). The first ranked network (score = 38, focus molecules = 18) (S3 Fig) was associated with cellular function and maintenance, humoral immune response and protein synthesis. Top functions of the other 5 highly significant networks were associated with drug metabolism, cell death and survival, organ morphology and cardiovascular system development and function.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: National Research Council (CNR), Institute of Clinical Physiology, Lecce, Italy.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus