[PP.36.09] MIRNA-REGULATED CARDIOVASCULAR PATHWAYS IN ESTRADIOL-TREATED HUMAN VEIN ENDOTHELIAL CELLS

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Abstract

Objective:

Endothelium, as target of estrogens, has a key role in the modulation of vascular physiology. MicroRNAs (miRNAs) are a small non-coding RNAs that modulate post-transcriptional expression of numerous genes implicated in a wide range of biological processes. Our aim was to determine cardiovascular pathways regulated by miRNA expression modification induced by estradiol in cultured human endothelial cells.

Design and method:

Primary HUVEC were exposed to 1 nM estradiol for 24 hours and miRNAs were isolated by miRNeasy Mini Kit (Qiagen). miRNAs expression was performed with GeneChip miRNA 4.0 Array (Affymetrix). Global differences between samples were measured by Principal Components Analysis (PCA) and changes in the expression profile were analyzed by Hierarchical Cluster using Partek Genomic Suite v6.6 software (Partek Inc., ST Louise, MO). Highly predicted and experimentally observed mRNA targets of differentially expressed miRNAs were used to canonical pathway analysis using Ingenuity Pathway Analysis software.

Results:

Global interrelationships among samples studied by PCA analysis shown differences between samples from control cells and estradiol-treated cells. We identified 120 miRNAs with significant differential expression: 47 up-regulated and 73 down-regulated with estradiol exposure. Bioinformatic analysis revealed significant canonical pathways important for endothelial function, including ERK/MAPK signalling, integrin signalling and actin cytoskeleton signalling, among other pathways.

Conclusions:

This study identifies changes in miRNA expression profile of human endothelial cells by which estradiol regulates different biological processes implicated in vascular function.

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