Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-9-14
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9150
pubmed:author
pubmed:issnType
Print
pubmed:volume
182
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-75
pubmed:dateRevised
2009-11-19
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
pubmed:year
2005
pubmed:articleTitle
JTT-705 blocks cell proliferation and angiogenesis through p38 kinase/p27(kip1) and Ras/p21(waf1) pathways.
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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't