Linked Life Data

12021169

Source:http://linkedlifedata.com/resource/pubmed/id/12021169

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-5-21
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2052-61
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12021169-Animals, pubmed-meshheading:12021169-Cells, Cultured, pubmed-meshheading:12021169-Endothelium, Vascular, pubmed-meshheading:12021169-Enzyme Activation, pubmed-meshheading:12021169-Enzyme Activators, pubmed-meshheading:12021169-Female, pubmed-meshheading:12021169-Humans, pubmed-meshheading:12021169-Immunoblotting, pubmed-meshheading:12021169-Mitogen-Activated Protein Kinases, pubmed-meshheading:12021169-Nitric Oxide, pubmed-meshheading:12021169-Nitric Oxide Synthase, pubmed-meshheading:12021169-Nitric Oxide Synthase Type III, pubmed-meshheading:12021169-Ovariectomy, pubmed-meshheading:12021169-Piperidines, pubmed-meshheading:12021169-Pregnancy, pubmed-meshheading:12021169-Rats, pubmed-meshheading:12021169-Rats, Wistar, pubmed-meshheading:12021169-Selective Estrogen Receptor Modulators
pubmed:year
2002
pubmed:articleTitle
Genomic and nongenomic mechanisms of nitric oxide synthesis induction in human endothelial cells by a fourth-generation selective estrogen receptor modulator.
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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't