Plasma flavanol metabolites modulate expression of miRNA in endothelial cells and affect post-transcriptional regulation of genes regulating adhesion and transendothelial migration

Abstract

National audienceMicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs and constitute a class of post-transcriptional regulators. We showed previously that flavanol metabolites decrease adhesion of monocytes to endothelial cells through modulation of expression of genes. The aim of this work was to identify the impact of flavanol metabolites at physiologically-relevant concentrations on the expression of miRNAs in endothelial cells. The use of microarrays revealed that 4’MEC, 4’MEC7G and EC4’S can modulate expression of miRNAs involved in the regulation of inflammation, cell adhesion or cell invasion, such as miR-221 or miR-181. These metabolites regulate the expression of different miRNAs that could exert post-transcriptional regulation of different target genes that are however involved in the same cellular pathways. These pathways mainly concern those involved in regulation of cell adhesion and transendothelial migration. Analyses of gene and protein expression of target genes revealed that miRNA could affect mRNA levels of certain genes, such as WASP1 and consequently the level of the protein, but also only decrease the translation and the protein quantity without affecting level of mRNA, as observed for BIRC2. In conclusion, these data provide an insight into new molecular mechanisms by which plasma flavanol metabolites at physiologically relevant concentrations may preserve vascular endothelium integrity