Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways
Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways
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DOI：
10.1002/mnfr.201300658
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发表时间：
2014-05-01
影响因子：
5.2
通讯作者：
Milenkovic, Dragan
中科院分区：
文献类型：
--
作者：
Claude, Sylvain;Boby, Celine;Milenkovic, Dragan
食用富含黄烷醇的食物与内皮功能的改善有关。然而，参与这种益处的特定生物活性黄烷醇代谢物及其作用的分子机制尚未确定。方法和结果4-O-甲基（-）-表儿茶素、4-O-甲基（-）-表儿茶素-7-β-d-葡糖苷酸和（-）表儿茶素-4-硫酸盐在生理相关浓度下降低单核细胞与内皮细胞的粘附，从0.2到1 M。转录组学研究表明，每种黄烷醇代谢产物影响内皮细胞中不同基因的表达。然而，这些基因参与控制单核细胞粘附和迁移至血管内皮的细胞过程，最显著的是那些调节细胞粘附、细胞-细胞连接、粘着斑和细胞骨架重塑的基因。获得的基因表达谱表明较低的单核细胞募集，与细胞粘附试验的结果一致。代谢产物的nutrogenomic效应似乎是通过其调节p65和p38细胞信号蛋白磷酸化的能力介导的。ConclusionOur study provides findings into molecular mechanisms by which plasma flavanol metabolites can be efficient to preserve vascular endothelial integrity in nutritional relevant conditions.
ScopeConsumption of flavanol-rich foods is associated with an improvement in endothelial function. However, the specific biologically active flavanol metabolites involved in this benefit, as well as their molecular mechanisms of action have not been identified. The aim of this work was to examine the effect of plasma flavanol metabolites on adhesion of monocytes to TNF--activated endothelial cells and identify potential underlying mechanisms.Methods and results4-O-methyl(-)-epicatechin, 4-O-methyl(-)-epicatechin-7--d-glucuronide, and (-)epicatechin-4-sulfate decreased the adhesion of monocytes to endothelial cells at physiologically relevant concentrations, from 0.2 to 1 M. Transcriptomic studies showed that each of the flavanol metabolites affected the expression of different genes in endothelial cells. However, these genes are involved in the cellular processes that control adhesion and migration of monocytes to vascular endothelium, most notably those regulating cell adhesion, cell-cell junctions, focal adhesion, and cytoskeleton remodeling. Gene expression profiles obtained suggest lower monocyte recruitment, in agreement with results from cell adhesion assays. The nutrigenomic effect of metabolites seems to be mediated through their capacity to modulate phosphorylation of p65 and p38 cell-signaling proteins.ConclusionOur study provides findings into the molecular mechanisms by which plasma flavanol metabolites could be efficient to preserve vascular endothelium integrity in nutritionally relevant conditions.