Estrogen Receptor Activation Protects Against TNF-α-Induced Endothelial Dysfunction. (January 2014)

• Record Type: Journal Article
• Authors: Palmieri, Daniela; Perego, Patrizia; Palombo, Domenico
• Is Part Of: Angiology. Volume 65:Number 1(2014)
• Page Start: 17
• Page End: 21
• Publication Date: 2014-01
• Subjects: apigenin -- endothelial dysfunction -- eNOS -- estrogen receptor -- MMP-9 -- TNF-α; Blood-vessels -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; 616.13005
• DOI: 10.1177/0003319713477909
• Languages: English
• ISSNs: 0003-3197

Abstract

Lack of estrogen is a cause of cardiovascular disease in men and postmenopausal women. We examined the effects of estrogen receptor (ERs) activation/inactivation on endothelial cells subjected to tumor necrosis factor (TNF) α, which is involved in vascular disease pathogenesis. Endothelial nitric oxide synthase (eNOS) and matrix metalloproteinases (MMP) 9 expression, as well as protein kinase B (PKB) activation were evaluated as markers of endothelial dysfunction. The TNF-α induces eNOS and MMP-9 expression and PKB activation. The ER activation by apigenin, a nonsteroidal compound with estrogen-like activity mediated through ER binding-dependent pathways, counteracts these effects. These effects are reversed by classic (ER-α and ER-β) and nonclassic (G-protein-coupled receptor) ER inhibitors (ICI182 780 and pertussis toxin, respectively). Our data suggest that ER activation counteracts endothelial dysfunction induced by TNF-α. The use of ER activators, such as apigenin, may represent a strategy to prevent vascular disease associated with endothelial dysfunction, while avoiding the feminizing effects of estrogens.