Abstract
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.
Methods and 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells / physiology
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Animals
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Aorta / injuries
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Aorta / metabolism
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Catheterization
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Cell Division / physiology
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Cell Movement / physiology
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Coronary Artery Disease / metabolism
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Coronary Artery Disease / pathology
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DNA / biosynthesis
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Fibroblast Growth Factor 2 / pharmacology
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Humans
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Ligands
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Mice
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Muscle, Smooth, Vascular / physiology
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Platelet-Derived Growth Factor / pharmacology
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RNA, Messenger / metabolism
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Rats
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Cytoplasmic and Nuclear / physiology*
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Subcellular Fractions / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Tunica Intima / metabolism
Substances
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Ligands
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Platelet-Derived Growth Factor
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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Fibroblast Growth Factor 2
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DNA