N-oleoylethanolamide suppresses intimal hyperplasia after balloon injury in rats through AMPK/PPARα pathway.
Biochem Biophys Res Commun
; 496(2): 415-421, 2018 02 05.
Article
em En
| MEDLINE
| ID: mdl-29305859
ABSTRACT
Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events in the pathological course of restenosis after percutaneous coronary intervention (PCI). N-oleoylethanolamide (OEA) is a bioactive lipid amide released upon dietary fat digestion with many reported actions. However, the effect of OEA on restenosis after vascular injury remains unknown. Here, we investigated the effects of OEA on intimal hyperplasia after balloon injury in vivo, its effect on VSMC proliferation and migration induced by platelet-derived growth factor (PDGF) stimulation in vitro, and the underlying mechanism underlying these effects. The results showed that OEA-treated rats displayed a significant reduction in neointima formation after balloon injury. In cultured VSMCs, treatment with OEA decreased cell proliferation and migration induced by PDGF. OEA treatment both in vivo and in vitro led to an increase in adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and peroxisome proliferator-activated receptor alpha (PPARα), and a decrease in proliferating cell nuclear antigen (PCNA) and cyclinD1 expression. Pharmacological inhibition of AMPK and PPARα reversed the suppressive effects of OEA on VSMC proliferation and migration, suggesting that the suppressive effect of OEA on VSMC proliferation and migration is mediated through the activation of AMPK and PPARα. In conclusion, our present study demonstrated that OEA attenuated neointima formation in response to balloon injury by suppressing SMC proliferation and migration through an AMPK and PPARα-dependent mechanism. Our data suggests that OEA may be a potential therapeutic agent for restenosis after PCI.
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Base de dados:
MEDLINE
Assunto principal:
Ácidos Oleicos
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Fármacos Cardiovasculares
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Lesões das Artérias Carótidas
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Endocanabinoides
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PPAR alfa
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Proteínas Quinases Ativadas por AMP
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Neointima
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Hiperplasia
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article