Aim: 

Estrogens induce a protective profile on basic vascular research, although clinical data are unclear and may contribute, for instance, to increase the risk of thrombosis. We investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) after treatment with 17beta-estradiol.

Methods: 

HUVEC were incubated in the presence or absence of estradiol (1 nM) for 24 hours. Total cellular RNA was extracted and global gene expression was studied with GeneChip Genome U133 Plus 2.0 microarrays. Changes in expression profiles were analyzed with dCHIP Analysis and SpotFire Decision Site software, followed by an ANOVA. False Discovery Rate was used to discriminate false positives in the multivariant system.

Results: 

364 genes were identified as differentially expressed between the two groups with 1.9-fold change threshold. Supervised Principal Component Analysis and Hierarchical Cluster analysis clearly revealed differences between control samples and samples treated with estradiol. The top-five canonical pathways significantly regulated by estrogen were notch signalling, actin cytoskeleton signalling, pentose phosphate pathway, axonal guidance signaling and integrin signalling. Microarray data were confirmed by quantitative RT-PCR in vascular meaning genes.

Conclusion: 

Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes.

Supported by Ministerio Ciencia e Innovación, ISCIII (FIS 06/0589, FIS 08/0634, RED HERACLES RD06/0009); Consellería Sanidad, GV (AP 09/2007, AP 121/08). PJO holds a post-doc position, and AS is a FPI fellow (BFPI 06/145), both from Consellería de Educación, Generalitat Valenciana, Spain.