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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2002-6-10
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pubmed:abstractText |
Peroxisome proliferator-activated receptors (PPARs) regulate lipid and glucose metabolism and exert several vascular effects that may provide a dual benefit of these receptors on metabolic disorders and atherosclerotic vascular disease. Endothelial cell migration is a key event in the pathogenesis of atherosclerosis. We therefore investigated the effects of lipid-lowering PPARalpha-activators (fenofibrate, WY14643) and antidiabetic PPARgamma-activators (troglitazone, ciglitazone) on this endothelial cell function. Both PPARalpha- and PPARgamma-activators significantly inhibited VEGF-induced migration of human umbilical vein endothelial cells (EC) in a concentration-dependent manner. Chemotactic signaling in EC is known to require activation of two signaling pathways: the phosphatidylinositol-3-kinase (PI3K)-->Akt- and the ERK1/2 mitogen-activated protein kinase (ERK MAPK) pathway. Using the pharmacological PI3K-inhibitor wortmannin and the ERK MAPK-pathway inhibitor PD98059, we observed a complete inhibition of VEGF-induced EC migration. VEGF-induced Akt phosphorylation was significantly inhibited by both PPARalpha- and gamma-activators. In contrast, VEGF-stimulated ERK MAPK-activation was not affected by any of the PPAR-activators, indicating that they inhibit migration either downstream of ERK MAPK or independent from this pathway. These results provide first evidence for the antimigratory effects of PPAR-activators in EC. By inhibiting EC migration PPAR-activators may protect the vasculature from pathological alterations associated with metabolic disorders.
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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/Chromans,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fenofibrate,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Hypolipidemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
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/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxisome Proliferators,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/ciglitazone,
http://linkedlifedata.com/resource/pubmed/chemical/pirinixic acid,
http://linkedlifedata.com/resource/pubmed/chemical/troglitazone
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
293
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1431-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12054675-Apoptosis,
pubmed-meshheading:12054675-Blotting, Western,
pubmed-meshheading:12054675-Cell Movement,
pubmed-meshheading:12054675-Cells, Cultured,
pubmed-meshheading:12054675-Chromans,
pubmed-meshheading:12054675-Endothelial Growth Factors,
pubmed-meshheading:12054675-Endothelium, Vascular,
pubmed-meshheading:12054675-Enzyme Inhibitors,
pubmed-meshheading:12054675-Fenofibrate,
pubmed-meshheading:12054675-Flavonoids,
pubmed-meshheading:12054675-Humans,
pubmed-meshheading:12054675-Hypoglycemic Agents,
pubmed-meshheading:12054675-Hypolipidemic Agents,
pubmed-meshheading:12054675-In Situ Nick-End Labeling,
pubmed-meshheading:12054675-Lipid Metabolism,
pubmed-meshheading:12054675-Lymphokines,
pubmed-meshheading:12054675-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12054675-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12054675-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12054675-Peroxisome Proliferators,
pubmed-meshheading:12054675-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12054675-Phosphorylation,
pubmed-meshheading:12054675-Pyrimidines,
pubmed-meshheading:12054675-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12054675-Signal Transduction,
pubmed-meshheading:12054675-Thiazoles,
pubmed-meshheading:12054675-Thiazolidinediones,
pubmed-meshheading:12054675-Time Factors,
pubmed-meshheading:12054675-Transcription Factors,
pubmed-meshheading:12054675-Umbilical Veins,
pubmed-meshheading:12054675-Vascular Endothelial Growth Factor A,
pubmed-meshheading:12054675-Vascular Endothelial Growth Factors,
pubmed-meshheading:12054675-Vasodilator Agents
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pubmed:year |
2002
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pubmed:articleTitle |
PPAR activators inhibit endothelial cell migration by targeting Akt.
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pubmed:affiliation |
Department of Medicine/Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. goetze@dhzb.be
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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