| pubmed-article:11711492 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C0026844 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C1135918 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C0132555 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C0360714 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:11711492 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:11711492 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:11711492 | pubmed:dateCreated | 2001-11-16 | lld:pubmed |
| pubmed-article:11711492 | pubmed:abstractText | Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase ameliorate atherosclerosis by both cholesterol-dependent and cholesterol-independent mechanisms. We examined whether HMG-CoA reductase inhibitors affect the expression and activity of inducible NO synthase (iNOS) in cultured rat aortic vascular smooth muscle (VSM) cells. Atorvastatin (34 to 68 micromol/L) markedly increased nitrite production, an increase that was essentially abrogated by the NO synthase inhibitor N(G)-monomethyl-L-arginine (500 micromol/L). Activity of iNOS, determined by the conversion of L-arginine to L-citrulline, increased 9-fold after atorvastatin treatment. Western blot and semiquantitative reverse transcriptase-polymerase chain reaction revealed that atorvastatin (34 to 68 micromol/L) strongly upregulated iNOS protein and mRNA levels, respectively. These concentrations of atorvastatin did not cause cytotoxicity, as judged by the cell survival rate. Similarly, simvastatin and lovastatin (34 micromol/L) caused robust upregulation of the iNOS protein level. Transfection experiments demonstrated that the -1034- to 88-bp human iNOS promoter was strongly induced by atorvastatin (34 micromol/L). Electromobility and supershift assays using a nuclear factor-kappaB (NF-kappaB) consensus oligonucleotide and nuclear extracts from VSM cells as well as transfection studies using an NF-kappaB reporter plasmid suggested that the transcriptional activation of the iNOS gene by atorvastatin is not mediated via the NF-kappaB pathway. We conclude that HMG-CoA reductase inhibitors potently upregulate iNOS expression and activity in VSM cells, at least in part, by transcriptional mechanisms that do not depend on transcription factor NF-kappaB. These effects might have important implications for the impact of HMG-CoA reductase inhibitors on atherosclerosis. | lld:pubmed |
| pubmed-article:11711492 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11711492 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11711492 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11711492 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:11711492 | pubmed:issn | 1524-4563 | lld:pubmed |
| pubmed-article:11711492 | pubmed:author | pubmed-author:MadiasN ENE | lld:pubmed |
| pubmed-article:11711492 | pubmed:author | pubmed-author:KolyadaA YAY | lld:pubmed |
| pubmed-article:11711492 | pubmed:author | pubmed-author:FedtsovAA | lld:pubmed |
| pubmed-article:11711492 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:11711492 | pubmed:volume | 38 | lld:pubmed |
| pubmed-article:11711492 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11711492 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11711492 | pubmed:pagination | 1024-9 | lld:pubmed |
| pubmed-article:11711492 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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| pubmed-article:11711492 | pubmed:year | 2001 | lld:pubmed |
| pubmed-article:11711492 | pubmed:articleTitle | 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors upregulate inducible NO synthase expression and activity in vascular smooth muscle cells. | lld:pubmed |
| pubmed-article:11711492 | pubmed:affiliation | Department of Medicine, Tufts University School of Medicine, Division of Nephrology and the Tupper Research Institute, New England Medical Center, Boston, Massachusetts, USA. | lld:pubmed |
| pubmed-article:11711492 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11711492 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
