| pubmed-article:12021169 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12021169 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:12021169 | lifeskim:mentions | umls-concept:C0225336 | lld:lifeskim |
| pubmed-article:12021169 | lifeskim:mentions | umls-concept:C0017428 | lld:lifeskim |
| pubmed-article:12021169 | lifeskim:mentions | umls-concept:C0732611 | lld:lifeskim |
| pubmed-article:12021169 | lifeskim:mentions | umls-concept:C1157570 | lld:lifeskim |
| pubmed-article:12021169 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:12021169 | lifeskim:mentions | umls-concept:C0441712 | lld:lifeskim |
| pubmed-article:12021169 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:12021169 | pubmed:dateCreated | 2002-5-21 | lld:pubmed |
| pubmed-article:12021169 | pubmed:abstractText | Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. EM-652 (acolbifene) is a fourth-generation selective ER modulator (SERM) exerting complete antiestrogenic effects on the breast and uterus. EM-652 potently inhibits bone resorption and induces positive lipid modifications in estrogen-deficient animals. As most of the cardioprotective actions of estrogen are exerted directly at the vascular level, we studied the effects of EM-652 on endothelial production of nitric oxide (NO) in vitro and in vivo. EM-652 triggers NO release by human umbilical vein endothelial cells through nongenomic mechanisms, rapidly activating endothelial nitric oxide synthase (eNOS) via an ER-dependent sequential activation of MAPKs and PI3K/Akt pathways independently from gene transcription or protein synthesis. Moreover, EM-652 increases eNOS protein levels during prolonged treatments. Upon pharmacological comparison, EM-652 is markedly more potent than the SERMs raloxifene and tamoxifen in increasing NO synthesis from endothelial cells. In ovariectomized and fertile rats, EM-652 increases aortic eNOS expression and enzymatic activity at low, but not at higher, dosages. The present data show that EM-652 (acolbifene) has estrogen-like activity on the vascular wall, directly increasing NO production through genomic and nongenomic mechanisms in vitro and in vivo. | lld:pubmed |
| pubmed-article:12021169 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12021169 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12021169 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12021169 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:12021169 | pubmed:issn | 0013-7227 | lld:pubmed |
| pubmed-article:12021169 | pubmed:author | pubmed-author:LabrieFernand... | lld:pubmed |
| pubmed-article:12021169 | pubmed:author | pubmed-author:SimonciniTomm... | lld:pubmed |
| pubmed-article:12021169 | pubmed:author | pubmed-author:LuisiMicheleM | lld:pubmed |
| pubmed-article:12021169 | pubmed:author | pubmed-author:GenazzaniAndr... | lld:pubmed |
| pubmed-article:12021169 | pubmed:author | pubmed-author:VaroneGaetano... | lld:pubmed |
| pubmed-article:12021169 | pubmed:author | pubmed-author:FornariLetizi... | lld:pubmed |
| pubmed-article:12021169 | pubmed:author | pubmed-author:MannellaPaolo... | lld:pubmed |
| pubmed-article:12021169 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12021169 | pubmed:volume | 143 | lld:pubmed |
| pubmed-article:12021169 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12021169 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12021169 | pubmed:pagination | 2052-61 | lld:pubmed |
| pubmed-article:12021169 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:12021169 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12021169 | pubmed:articleTitle | Genomic and nongenomic mechanisms of nitric oxide synthesis induction in human endothelial cells by a fourth-generation selective estrogen receptor modulator. | lld:pubmed |
| pubmed-article:12021169 | pubmed:affiliation | Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, 56100 Pisa, Italy. t.simoncini@obgyn.med.unipi.it | lld:pubmed |
| pubmed-article:12021169 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12021169 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12021169 | lld:pubmed |
