Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation.

Détails

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Etat: Serval
Version: Final published version
ID Serval
serval:BIB_B6DBB9BD5672
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation.
Périodique
Journal of lipid research
Auteur(s)
Molica F., Burger F., Thomas A., Staub C., Tailleux A., Staels B., Pelli G., Zimmer A., Cravatt B., Matter C.M., Pacher P., Steffens S.
ISSN
1539-7262 (Electronic)
ISSN-L
0022-2275
Statut éditorial
Publié
Date de publication
05/2013
Peer-reviewed
Oui
Volume
54
Numéro
5
Pages
1360-1368
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Percutaneous transluminal angioplasty is frequently used in patients with severe arterial narrowing due to atherosclerosis. However, it induces severe arterial injury and an inflammatory response leading to restenosis. Here, we studied a potential activation of the endocannabinoid system and the effect of FA amide hydrolase (FAAH) deficiency, the major enzyme responsible for endocannabinoid anandamide degradation, in arterial injury. We performed carotid balloon injury in atherosclerosis-prone apoE knockout (apoE(-/-)) and apoE(-/-)FAAH(-/-) mice. Anandamide levels were systemically elevated in apoE(-/-) mice after balloon injury. ApoE(-/-)FAAH(-/-) mice had significantly higher baseline anandamide levels and enhanced neointima formation compared with apoE(-/-) controls. The latter effect was inhibited by treatment with CB1 antagonist AM281. Similarly, apoE(-/-) mice treated with AM281 had reduced neointimal areas, reduced lesional vascular smooth-muscle cell (SMC) content, and proliferating cell counts. The lesional macrophage content was unchanged. In vitro proliferation rates were significantly reduced in CB1(-/-) SMCs or when treating apoE(-/-) or apoE(-/-)FAAH(-/-) SMCs with AM281. Macrophage in vitro adhesion and migration were marginally affected by CB1 deficiency. Reendothelialization was not inhibited by treatment with AM281. In conclusion, endogenous CB1 activation contributes to vascular SMC proliferation and neointima formation in response to arterial injury.

Mots-clé
Amidohydrolases/genetics, Amidohydrolases/metabolism, Animals, Apolipoproteins E/genetics, Apolipoproteins E/metabolism, Atherosclerosis/genetics, Atherosclerosis/metabolism, Atherosclerosis/pathology, Cell Proliferation, Humans, Mice, Mice, Knockout, Morpholines/pharmacology, Muscle, Smooth, Vascular/cytology, Muscle, Smooth, Vascular/drug effects, Muscle, Smooth, Vascular/metabolism, Neointima/genetics, Neointima/metabolism, Pyrazoles/pharmacology, Receptor, Cannabinoid, CB1/deficiency, Receptor, Cannabinoid, CB1/genetics, Receptor, Cannabinoid, CB1/metabolism, Tunica Intima/drug effects, Tunica Intima/injuries, Tunica Intima/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/01/2015 17:49
Dernière modification de la notice
09/05/2019 0:11
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