Effect of 17β-Estradiol on Endothelial Cell Expression of Inflammation-Related MicroRNA.

Introduction/ Objective: Estrogen plays a protective role in vascular health due, in part, to its regulation of endothelial inflammation. However, the mechanism(s) by which estrogen negatively regulates inflammatory signaling pathways is not completely understood. MicroRNAs (miRNAs) are recognized as sensitive and selective regulators of cardiovascular function, inflammation, and disease, yet the effects of 17β-estradiol on the endothelial miRNA profile are largely unknown. The aim of this study was to determine the effect of 17β-estradiol on the expression of inflammation-associated miRNAs in endothelial cells in vitro.

Methods: Human Umbilical Vein Endothelial cells (HUVECs) were treated with media in the absence (control) and presence of 17β-estradiol (100 nM) for 24 hr. Thereafter, endothelial cell release of cytokines (IL-6 and IL-8), the intracellular expression of the central protein inflammatory mediator NF- B, and the levels of inflammatory-associated miRNAs: miR-126, miR-146a, miR-181b, miR-204, and miR-let-7a, were determined.

Results: 17β-estradiol-treated cells released significantly lower levels of IL-6 (47.6±1.5 pg/mL vs 59.3±4.9 pg/mL) and IL-8 (36.3±2.3 pg/mL vs 44.0±2.0 pg/mL). Cellular expression of total NF- B (26.0±2.8 AU vs 21.2±3.1 AU) was not different between groups; however, activated NF- B (Ser536) (12.9±1.7 AU vs 20.2±2.2 AU) was markedly reduced in 17β-estradiol-treated cells as compared to untreated cells. Furthermore, cellular expressions of miR-126 (1.8±0.3 fold), miR-146a (1.7±0.3 fold), miR-181b (2.1±0.4 fold), miR-204 (1.9±0.4 fold), and miR-Let-7a (1.8±0.3 fold) were markedly increased in response to 17β-estradiol treatment.

Conclusion: These data suggest that the anti-inflammatory effect of 17β-estradiol in endothelial cells may be mediated by miRNAs.