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
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.
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.
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