Expression and function of PPARgamma in rat and human vascular smooth muscle cells.
BACKGROUND
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is activated by fatty acids, eicosanoids, and insulin-sensitizing thiazolidinediones (TZDs). The TZD troglitazone (TRO) inhibits vascular smooth muscle cell (VSMC) proliferation and migration in vitro and in postinjury intimal hyperplasia.


RESULTS
Rat and human VSMCs express mRNA and nuclear receptors for PPARgamma1. Three PPARgamma ligands, the TZDs TRO and rosiglitazone and the prostanoid 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), all inhibited VSMC proliferation and migration. PPARgamma is upregulated in rat neointima at 7 days and 14 days after balloon injury and is also present in early human atheroma and precursor lesions.


CONCLUSIONS
Pharmacological activation of PPARgamma expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis. These receptors are upregulated during vascular injury.
Law
R E
RE
Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, CA 90095, USA.
Goetze
S
S
Xi
X P
XP
Jackson
S
S
Kawano
Y
Y
Demer
L
L
Fishbein
M C
MC
Meehan
W P
WP
Hsueh
W A
WA
D016475:3T3 Cells / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000293:injuries / Q000378:metabolism; D002404:Catheterization; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism
D008024:Ligands; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D004247:DNA