RESEARCH ARTICLE


Cannabinoid Receptor 2 Deficiency in Haematopoietic cells Aggravates Early Atherosclerosis in LDL Receptor Deficient Mice



Dianne J.M Delsing1, *, Frank P Leijten1, Karin Arts1, Hans van Eenennaam1, Anja Garritsen1, Marion J.J Gijbels2, 3, Menno P.J de Winther2, Andrea van Elsas1
1 MSD, Department of Immune Therapeutics, Oss, The Netherlands
2 Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
3 Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands


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© Delsing et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Immune Therapeutics, Oss, The Netherlands; Tel: +31 412 66 3360; Fax: +31 412 66 2553; E-mail: dianne.delsing@merck.com


Abstract

Objective:

The cannabinoid receptor 2 (CB2) has been implicated to play a role in various inflammatory processes. Since atherosclerosis is currently considered a chronic inflammatory disease, we studied the effect of haematopoietic CB2 deficiency on atherosclerosis development.

Methods and results:

To investigate the effect of CB2 deficiency in immune cells on atherogenesis in vivo, a bone marrow transplantation was performed in irradiated LDL receptor deficient mice (LDLr-/-), using CB2 deficient (CB2-/-) or wildtype (WT) donor mice. After 12 weeks on a high fat-high cholesterol diet, en face analysis showed that atherosclerosis in the aortic arch was significantly increased in CB2-/- transplanted animals (6.40 ± 3.21%) as compared to WT transplanted mice (3.85 ± 1.61%). Although the total lesion area in the aortic root was not significantly different between WT and CB2-/- transplanted mice (0.45 ± 0.13 mm2 and 0.51 ± 0.17 mm2, respectively), CB2-/- transplanted mice showed a significantly larger plaque area (0.13 ± 0.07 mm2) than WT transplanted mice (0.08 ± 0.05 mm2) in the aortic valve in which atherogenesis is in an earlier stage than in the other aortic valves.

Conclusions:

Lack of endocannabinoid signaling via the CB2 receptor aggravates early atherosclerosis development in LDLr-/- mice, suggesting that CB2 specific activation may prevent the development of atherosclerosis.

Keywords: Atherosclerosis, cannabinoid receptor, CB2, LDLr-/- mice..