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Atheroprotection via cannabinoid receptor-2 is mediated by circulating and vascular cells in vivo.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2011 Dec; Vol. 51 (6), pp. 1007-14. Date of Electronic Publication: 2011 Aug 18. - Publication Year :
- 2011
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Abstract
- Low-dose oral tetrahydrocannabinol (THC) reduces progression of atherosclerosis in mice. THC activates central cannabinoid-1 receptors (CB1) with subsequent psychoactive effects as well as peripheral cannabinoid-2 receptors (CB2). In order to dissect the underlying mechanisms, we performed experiments under selective CB2 stimulation as well as after genetic disruption of the CB2 receptor. Atherosclerosis prone apolipoprotein E-deficient mice were crossed with cannabinoid receptor-2 deficient mice to obtain ApoE -/- CB2 -/- double knockout mice. After 8weeks of a high-cholesterol diet, immunohistochemical stainings of the aortic root revealed that vascular leukocyte infiltration in atherosclerotic plaques was accelerated in ApoE -/- CB2 -/- mice compared with ApoE -/- mice. This was accompanied by increased release of reactive oxygen species as measured using L012-enhanced chemiluminescence, and by decreased endothelial function as assessed in isolated aortic rings in organ chamber experiments. ApoE -/- mice treated with the selective CB2 agonist JWH 133 during a high-cholesterol diet showed decreased atherosclerotic lesion formation, improved endothelial function and reduced levels of reactive oxygen species. To assess whether CB2 expression in circulating cells influences atherosclerosis, irradiated ApoE -/- mice were repopulated with bone marrow-derived cells from ApoE -/- and ApoE -/- CB2 -/- mice and were fed a high-cholesterol diet for 8weeks. CB2 deficiency in bone marrow-derived cells increased leukocyte infiltration into the vessel wall, but had no impact on plaque formation. Cell culture experiments revealed that CB2 activation diminishes ROS generation in vascular cells. Selective CB2 receptor stimulation modulates atherogenesis via impact on both circulating proinflammatory and vascular cells.<br /> (2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Apolipoproteins E genetics
Atherosclerosis pathology
Atherosclerosis prevention & control
Blood Pressure
Bone Marrow Transplantation
Cannabinoid Receptor Modulators metabolism
Cholesterol blood
Endothelial Cells metabolism
Endothelium metabolism
Heart Rate
Leukocytes metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Reactive Oxygen Species metabolism
Receptor, Cannabinoid, CB2 genetics
Atherosclerosis metabolism
Receptor, Cannabinoid, CB2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8584
- Volume :
- 51
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 21884703
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2011.08.008