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

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_B6DBB9BD5672
Type
Article: article from journal or magazin.
Collection
Publications
Title
Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation.
Journal
Journal of lipid research
Author(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
Publication state
Published
Issued date
05/2013
Peer-reviewed
Oui
Volume
54
Number
5
Pages
1360-1368
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.

Keywords
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
Yes
Create date
21/01/2015 16:49
Last modification date
20/08/2019 15:25
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