Prostacyclin synthase gene transfer inhibits neointimal formation by suppressing PPAR delta expression
| Autor: | Masakazu Ishii, Yasushi Numaguchi, Kenji Okumura, Toyoaki Murohara, Takahisa Kondo, Yasuhiro Ogawa, Kazuhiko Yokouchi, Ryuji Kubota, Hajime Imai |
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| Rok vydání: | 2006 |
| Předmět: |
MAPK/ERK pathway
Neointima Male medicine.medical_specialty Endothelium p38 mitogen-activated protein kinases Myocytes Smooth Muscle Down-Regulation Prostacyclin p38 Mitogen-Activated Protein Kinases Muscle Smooth Vascular Prostacyclin synthase Adenoviridae Cytochrome P-450 Enzyme System Internal medicine medicine Animals Humans PPAR delta Phosphorylation Aorta Cells Cultured biology Kinase Angioplasty Gene Transfer Techniques Epoprostenol Cell biology Rats Intramolecular Oxidoreductases medicine.anatomical_structure Endocrinology cardiovascular system biology.protein Peroxisome proliferator-activated receptor delta Cardiology and Cardiovascular Medicine Carotid Artery Injuries Tunica Intima medicine.drug |
| Zdroj: | Atherosclerosis. 195(2) |
| ISSN: | 1879-1484 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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