Abstract
Objective
Prostacyclin (PGI2) is a potent ligand of peroxisome proliferator-activated receptor δ (PPARδ) that
regulates cell growth and differentiation. The aim of this study was to elucidate
how endogenous PGI2 overexpression affects the expressions of PPARδ and mitogen-activated protein kinases
(MAPKs) in the development of neointimal formation in experimental angioplasty with
adenovirus-mediated PGI2 synthase (Ad-PGIS) gene transfer.
Methods and results
In human aortic smooth muscle cells, protein blotting analysis showed that PGI2 overproduction decreased the levels of phosphorylated p38 MAPK (P-p38 MAPK) (2.0-fold
versus 0.83-fold relative to control). Immunohistochemical analysis in balloon-injured
arteries revealed diffuse expression of PPARδ in the neointima of control vessels,
with no expression in uninjured vessels. The level of PPARδ expression was lower in
Ad-PGIS-treated arteries than in control vessels, with the PPARδ localized in the
neointima adjacent to endothelium. Staining of P-p38 MAPK showed a similar pattern
to PPARδ among the three groups. Morphometric analysis at day 14 revealed that Ad-PGIS
reduced the intima-to-media ratio by up to 59%.
Conclusions
Ad-PGIS gene transfer reduced PPARδ expression and inhibited neointimal formation
after balloon injury in accordance with the reduction in the phosphorylation of p38
MAPK.
Keywords
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Article info
Publication history
Published online: February 14, 2007
Accepted:
January 9,
2007
Received in revised form:
December 20,
2006
Received:
April 27,
2006
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
