Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1999-4-29
pubmed:abstractText
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that functions as a transcription factor to mediate ligand-dependent transcriptional regulation. Activation of PPARgamma by the naturally occurring ligand, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), or members of a new class of oral antidiabetic agents, e.g. BRL49653 and ciglitizone, has been linked to adipocyte differentiation, regulation of glucose homeostasis, inhibition of macrophage and monocyte activation, and inhibition of tumor cell proliferation. Here we report that human umbilical vein endothelial cells (HUVEC) express PPARgamma mRNA and protein. Activation of PPARgamma by the specific ligands 15d-PGJ2, BRL49653, or ciglitizone, dose dependently suppresses HUVEC differentiation into tube-like structures in three-dimensional collagen gels. In contrast, specific PPARalpha and -beta ligands do not affect tube formation although mRNA for these receptors are expressed in HUVEC. PPARgamma ligands also inhibit the proliferative response of HUVEC to exogenous growth factors. Treatment of HUVEC with 15d-PGJ2 also reduced mRNA levels of vascular endothelial cell growth factor receptors 1 (Flt-1) and 2 (Flk/KDR) and urokinase plasminogen activator and increased plasminogen activator inhibitor-1 (PAI-1) mRNA. Finally, administration of 15d-PGJ2 inhibited vascular endothelial cell growth factor-induced angiogenesis in the rat cornea. These observations demonstrate that PPARgamma ligands are potent inhibitors of angiogenesis in vitro and in vivo, and suggest that PPARgamma may be an important molecular target for the development of small-molecule inhibitors of angiogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9116-21
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:10085162-Animals, pubmed-meshheading:10085162-Cell Differentiation, pubmed-meshheading:10085162-Cell Division, pubmed-meshheading:10085162-Cells, Cultured, pubmed-meshheading:10085162-Cornea, pubmed-meshheading:10085162-Eicosanoids, pubmed-meshheading:10085162-Endothelium, Vascular, pubmed-meshheading:10085162-Gene Expression Regulation, pubmed-meshheading:10085162-Humans, pubmed-meshheading:10085162-Ligands, pubmed-meshheading:10085162-Neovascularization, Physiologic, pubmed-meshheading:10085162-Prostaglandin D2, pubmed-meshheading:10085162-RNA, Messenger, pubmed-meshheading:10085162-Rats, pubmed-meshheading:10085162-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:10085162-Thiazoles, pubmed-meshheading:10085162-Thiazolidinediones, pubmed-meshheading:10085162-Transcription Factors
pubmed:year
1999
pubmed:articleTitle
Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo.
pubmed:affiliation
Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080, USA.
pubmed:publicationType
Journal Article