Limits...
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.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.Such unbiased identification should increase our understanding of mechanisms by which n-3 fatty acids affect human diseases.

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

Experimental design and primary conclusions of the study.Abbreviations: EC, endothelial cells; DHA, docosahexaenoic acid; IL-1, interleukin-1 β.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482638&req=5

pone.0129652.g001: Experimental design and primary conclusions of the study.Abbreviations: EC, endothelial cells; DHA, docosahexaenoic acid; IL-1, interleukin-1 β.

Mentions: We had previously shown that DHA, starting from 25 μmol/L for 48 h, inhibited endothelial adhesion molecule expression, without endothelial toxicity, in a setting compatible with that of maximal DHA uptake and incorporation into endothelial cell membrane phospholipids [14]. All experiments were therefore performed accordingly. Comparative analysis of DHA-treated cells and untreated control cells identified that less than 1% of interrogated genes are significantly regulated, half of which (96 genes) were increased in expression and the rest (92 genes) were decreased (Fig 1). In contrast, 3 h stimulation with IL-1β 5 ng/mL affected a much higher number of genes, with 6.5% of the assayed gene sequences resulting in significant changes, with increased expression of 1034 genes and decreased expression of 997 other genes (Fig 1). Globally, treatment with DHA before IL-1β stimulation altered the expression of more than 2% of the IL-1β regulated genes (Fig 1).


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)

Experimental design and primary conclusions of the study.Abbreviations: EC, endothelial cells; DHA, docosahexaenoic acid; IL-1, interleukin-1 β.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129652.g001: Experimental design and primary conclusions of the study.Abbreviations: EC, endothelial cells; DHA, docosahexaenoic acid; IL-1, interleukin-1 β.
Mentions: We had previously shown that DHA, starting from 25 μmol/L for 48 h, inhibited endothelial adhesion molecule expression, without endothelial toxicity, in a setting compatible with that of maximal DHA uptake and incorporation into endothelial cell membrane phospholipids [14]. All experiments were therefore performed accordingly. Comparative analysis of DHA-treated cells and untreated control cells identified that less than 1% of interrogated genes are significantly regulated, half of which (96 genes) were increased in expression and the rest (92 genes) were decreased (Fig 1). In contrast, 3 h stimulation with IL-1β 5 ng/mL affected a much higher number of genes, with 6.5% of the assayed gene sequences resulting in significant changes, with increased expression of 1034 genes and decreased expression of 997 other genes (Fig 1). Globally, treatment with DHA before IL-1β stimulation altered the expression of more than 2% of the IL-1β regulated genes (Fig 1).

Bottom Line: High intakes of n-3 fatty acids exert anti-inflammatory effects and cardiovascular protection, but the underlying molecular basis is incompletely defined.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.Such unbiased identification should increase our understanding of mechanisms by which n-3 fatty acids affect human diseases.

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