Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation
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 eff...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-05-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752042173X |
| _version_ | 1818920467863437312 |
|---|---|
| author | Filippo Molica Fabienne Burger Aurélien Thomas Christian Staub Anne Tailleux Bart Staels Graziano Pelli Andreas Zimmer Benjamin Cravatt Christian M. Matter Pal Pacher Sabine Steffens |
| author_facet | Filippo Molica Fabienne Burger Aurélien Thomas Christian Staub Anne Tailleux Bart Staels Graziano Pelli Andreas Zimmer Benjamin Cravatt Christian M. Matter Pal Pacher Sabine Steffens |
| author_sort | Filippo Molica |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T01:22:13Z |
| format | Article |
| id | doaj.art-39d48e3595a542cb9629abab737a3408 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T01:22:13Z |
| publishDate | 2013-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-39d48e3595a542cb9629abab737a34082022-12-21T19:58:23ZengElsevierJournal of Lipid Research0022-22752013-05-0154513601368Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formationFilippo Molica0Fabienne Burger1Aurélien Thomas2Christian Staub3Anne Tailleux4Bart Staels5Graziano Pelli6Andreas Zimmer7Benjamin Cravatt8Christian M. Matter9Pal Pacher10Sabine Steffens11Division of Cardiology, University Hospital, Geneva, SwitzerlandDivision of Cardiology, University Hospital, Geneva, SwitzerlandUnit of Toxicology, University Center of Legal Medicine, Geneva, SwitzerlandUnit of Toxicology, University Center of Legal Medicine, Geneva, SwitzerlandEuropean Genomic Institute for Diabetes, FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, FranceEuropean Genomic Institute for Diabetes, FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, FranceDivision of Cardiology, University Hospital, Geneva, SwitzerlandINSERM UMR 1011 F-59000 Lille, France; Institut Pasteur de Lille, F-59000 Lille, France, Institute of Molecular Psychiatry, University of Bonn, GermanyThe Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, CACardiovascular Research, Institute of Physiology, Zurich Center for Integrative Human Physiology, University of ZurichCardiology, University Hospital, Zurich, Switzerland, Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institutes of Health, Bethesda, MDTo whom correspondence should be addressed sabine.steffens@med.uni-muenchen.de; Division of Cardiology, University Hospital, Geneva, Switzerland; Institute of Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, GermanyPercutaneous 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.http://www.sciencedirect.com/science/article/pii/S002222752042173Xrestenosisballoon injuryfatty acid amide hydrolase |
| spellingShingle | Filippo Molica Fabienne Burger Aurélien Thomas Christian Staub Anne Tailleux Bart Staels Graziano Pelli Andreas Zimmer Benjamin Cravatt Christian M. Matter Pal Pacher Sabine Steffens Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation Journal of Lipid Research restenosis balloon injury fatty acid amide hydrolase |
| title | Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation |
| title_full | Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation |
| title_fullStr | Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation |
| title_full_unstemmed | Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation |
| title_short | Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation |
| title_sort | endogenous cannabinoid receptor cb1 activation promotes vascular smooth muscle cell proliferation and neointima formation |
| topic | restenosis balloon injury fatty acid amide hydrolase |
| url | http://www.sciencedirect.com/science/article/pii/S002222752042173X |
| work_keys_str_mv | AT filippomolica endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT fabienneburger endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT aurelienthomas endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT christianstaub endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT annetailleux endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT bartstaels endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT grazianopelli endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT andreaszimmer endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT benjamincravatt endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT christianmmatter endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT palpacher endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation AT sabinesteffens endogenouscannabinoidreceptorcb1activationpromotesvascularsmoothmusclecellproliferationandneointimaformation |