rdf:type |
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lifeskim:mentions |
umls-concept:C0031727,
umls-concept:C0249197,
umls-concept:C0288472,
umls-concept:C0302600,
umls-concept:C0596290,
umls-concept:C0916168,
umls-concept:C1332737,
umls-concept:C1366876,
umls-concept:C1420626,
umls-concept:C1533157,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1833235
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pubmed:issue |
2
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pubmed:dateCreated |
2005-9-14
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pubmed:abstractText |
The excessive proliferation and migration of vascular smooth muscle cells (SMCs) participate in the growth and instability of atherosclerotic plaque. We examined the direct role of a newly developed chemical inhibitor of cholesteryl ester transfer protein, JTT-705, on SMC proliferation and angiogenesis in endothelial cells (ECs). JTT-705 inhibited human coronary artery SMC proliferation. JTT-705 induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular-signal-regulated kinases (ERK) in SMCs. In addition, the anti-proliferative effects of JTT-705 in SMCs were blocked by p38 MAPK inhibitor. JTT-705 induced the upregulation of p-p21(waf1), and this effect was blocked by dominant-negative Ras (N17), but not by inhibitors of p38 MAPK or ERK. In addition, JTT-705 also induced the upregulation of p27(kip1), and this effect was blocked by p38 MAPK inhibitor. Interestingly, culture medium from JTT-705-treated SMCs blocked human coronary artery EC tube formation in an in vitro model of angiogenesis indirectly via a decrease in vascular endothelial growth factor (VEGF) from SMCs and directly via an anti-proliferative effect in ECs. JTT-705 blocked the proliferation of SMCs through the activation of p38 kinase/p27(kip1) and Ras/p21(waf1) pathways, and simultaneously blocked EC tube formation associated with a decrease in VEGF production from SMCs and an anti-proliferative effect in ECs. Our results indicate that JTT-705 may induce a direct anti-atherogenic effect in addition to its inhibitory effect of CETP activity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203580,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/dalcetrapib,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9150
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
182
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
267-75
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16159599-Atherosclerosis,
pubmed-meshheading:16159599-Cell Division,
pubmed-meshheading:16159599-Cells, Cultured,
pubmed-meshheading:16159599-Coronary Vessels,
pubmed-meshheading:16159599-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:16159599-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:16159599-Endothelium, Vascular,
pubmed-meshheading:16159599-Enzyme Inhibitors,
pubmed-meshheading:16159599-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:16159599-Flavonoids,
pubmed-meshheading:16159599-Humans,
pubmed-meshheading:16159599-Imidazoles,
pubmed-meshheading:16159599-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16159599-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:16159599-MAP Kinase Signaling System,
pubmed-meshheading:16159599-Muscle, Smooth, Vascular,
pubmed-meshheading:16159599-Neovascularization, Pathologic,
pubmed-meshheading:16159599-Pyridines,
pubmed-meshheading:16159599-Sulfhydryl Compounds,
pubmed-meshheading:16159599-Up-Regulation,
pubmed-meshheading:16159599-Vascular Endothelial Growth Factor A,
pubmed-meshheading:16159599-p38 Mitogen-Activated Protein Kinases,
pubmed-meshheading:16159599-ras Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
JTT-705 blocks cell proliferation and angiogenesis through p38 kinase/p27(kip1) and Ras/p21(waf1) pathways.
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pubmed:affiliation |
Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-Ku, Fukuoka 814-0180, Japan. miuras@cis.fukuoka-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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