title: Estrogen receptor activation protects against TNF-α-induced endothelial dysfunction.
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.
authors: 1Vascular and Endovascular Unit, Laboratory of Clinical and Experimental Vascular Biology, DISC, University Hospital IRCCS San Martino, Italy.
authors: Daniela
authors: D
authors: Palmieri
authors: Patrizia
authors: P
authors: Perego
authors: Domenico
authors: D
authors: Palombo
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D047310:Apigenin; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9
keywords: MMP-9; TNF-α; apigenin; eNOS; endothelial dysfunction; estrogen receptor