1. Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation
- Author
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Pal Pacher, Christian M. Matter, Fabienne Burger, Sabine Steffens, Aurélien Thomas, Bart Staels, Graziano Pelli, Benjamin F. Cravatt, Anne Tailleux, Andreas Zimmer, Filippo Molica, and Christian Staub
- Subjects
Neointima ,medicine.medical_specialty ,Cannabinoid receptor ,Vascular smooth muscle ,Morpholines ,QD415-436 ,030204 cardiovascular system & hematology ,Biochemistry ,Muscle, Smooth, Vascular ,Amidohydrolases ,restenosis ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Apolipoproteins E ,0302 clinical medicine ,Endocrinology ,Receptor, Cannabinoid, CB1 ,Restenosis ,balloon injury ,Fatty acid amide hydrolase ,Internal medicine ,fatty acid amide hydrolase ,medicine ,Animals ,Humans ,Receptor ,Research Articles ,Cell Proliferation ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Chemistry ,Cell Biology ,Anandamide ,Atherosclerosis ,medicine.disease ,Endocannabinoid system ,3. Good health ,Surgery ,Amidohydrolases/genetics ,Amidohydrolases/metabolism ,Apolipoproteins E/genetics ,Apolipoproteins E/metabolism ,Atherosclerosis/genetics ,Atherosclerosis/metabolism ,Atherosclerosis/pathology ,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 ,nervous system ,cardiovascular system ,Pyrazoles ,lipids (amino acids, peptides, and proteins) ,Tunica Intima ,psychological phenomena and processes - 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.
- Published
- 2013
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