Source:http://linkedlifedata.com/resource/pubmed/id/12621163
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2003-3-6
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pubmed:abstractText |
We recently reported that lysophosphatidylcholine (lysoPC) acts on vascular smooth muscle cells ( VSMCs ) to produce a mitogenic response through the activation of extracellular signal-regulated kinases 1/2 (ERK1/2). In this study, we examined the role of HMG-CoA reductase inhibitors on lysoPC-induced VSMC proliferation. Pitavastatin, a new HMG-CoA reductase inhibitor, suppressed lysoPC-induced DNA synthesis in primary cultured rat VSMCs. Since lysoPC-induced ERK1/2 activation contributes to smooth muscle cell proliferation, we explored the effect of pitavastatin on ERK1/2 activation. Pitavastatin inhibited lysoPC-induced ERK1/2 phosphorylation and ERK1/2 activation. The other HMG-CoA reductase inhibitors, atrovastatin and fluvastatin, also inhibited lysoPC-induced ERK1/2 phosphorylation. Pitavastatin also inhibited lysoPC-induced c-fos mRNA expression. To gain insight into the mechanism of the inhibitory effect of pitavastatin on ERK1/2 activation by lysoPC, we examined the role of the mevalonate pathways. Mevalonate and farnesylpyrophosphate reduced the inhibition of ERK1/2 phosphorylation by pitavastatin. These studies demonstrate that pitavastatin may inhibit lysoPC-induced VSMC proliferation, at least in part, by inactivating ERK1/2, which is linked to mevalonate metabolism.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/pitavastatin
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pubmed:status |
MEDLINE
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pubmed:issn |
1340-3478
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37-42
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12621163-Animals,
pubmed-meshheading:12621163-Aorta, Thoracic,
pubmed-meshheading:12621163-Cattle,
pubmed-meshheading:12621163-Cell Division,
pubmed-meshheading:12621163-Cells, Cultured,
pubmed-meshheading:12621163-Enzyme Inhibitors,
pubmed-meshheading:12621163-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:12621163-Immunoblotting,
pubmed-meshheading:12621163-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12621163-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12621163-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12621163-Muscle, Smooth, Vascular,
pubmed-meshheading:12621163-Phosphorylation,
pubmed-meshheading:12621163-Quinolines
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pubmed:year |
2003
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pubmed:articleTitle |
Pitavastatin inhibits vascular smooth muscle cell proliferation by inactivating extracellular signal-regulated kinases 1/2.
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pubmed:affiliation |
Department of Endocrinology and Diabetes, Yokohama City University Medical Center, Yokohama, Japan. yamakat@urahp.yokohama-cu.ac.jp
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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