Nature, 2005-04, Vol.434 (7034), p.782-786
2005
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- Autor(en) / Beteiligte
- Titel
- Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice
- Ist Teil von
- Nature, 2005-04, Vol.434 (7034), p.782-786
- Ort / Verlag
- London: Nature Publishing
- Erscheinungsjahr
- 2005
- Quelle
- Psychology and Behavioral Sciences Collection
- Beschreibungen/Notizen
- Atherosclerosis is a chronic inflammatory disease, and is the primary cause of heart disease and stroke in Western countries. Derivatives of cannabinoids such as delta-9-tetrahydrocannabinol (THC) modulate immune functions and therefore have potential for the treatment of inflammatory diseases. We investigated the effects of THC in a murine model of established atherosclerosis. Oral administration of THC (1 mg kg-1 per day) resulted in significant inhibition of disease progression. This effective dose is lower than the dose usually associated with psychotropic effects of THC. Furthermore, we detected the CB2 receptor (the main cannabinoid receptor expressed on immune cells) in both human and mouse atherosclerotic plaques. Lymphoid cells isolated from THC-treated mice showed diminished proliferation capacity and decreased interferon-γ secretion. Macrophage chemotaxis, which is a crucial step for the development of atherosclerosis, was also inhibited in vitro by THC. All these effects were completely blocked by a specific CB2 receptor antagonist. Our data demonstrate that oral treatment with a low dose of THC inhibits atherosclerosis progression in the apolipoprotein E knockout mouse model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells. Thus, THC or cannabinoids with activity at the CB2 receptor may be valuable targets for treating atherosclerosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/nature03389Titel-ID: cdi_proquest_miscellaneous_67720846
- Format
- –
- Schlagworte
- Animals, Apolipoproteins E - deficiency, Apolipoproteins E - genetics, Arteriosclerosis - complications, Arteriosclerosis - drug therapy, Arteriosclerosis - immunology, Arteriosclerosis - pathology, Atherosclerosis (general aspects, experimental research), Biological and medical sciences, Blood and lymphatic vessels, Cardiology. Vascular system, Cells, Cultured, Chemotaxis, Leukocyte - drug effects, Disease Models, Animal, Disease Progression, Dronabinol - administration & dosage, Dronabinol - pharmacology, Dronabinol - therapeutic use, Humans, Inflammation - complications, Inflammation - drug therapy, Inflammation - immunology, Inflammation - pathology, Interferon-gamma - pharmacology, Interferon-gamma - secretion, Macrophages - cytology, Macrophages - drug effects, Macrophages - immunology, Macrophages - metabolism, Medical sciences, Mice, Mice, Knockout, Receptor, Cannabinoid, CB2 - antagonists & inhibitors, Receptor, Cannabinoid, CB2 - metabolism, Receptors, CCR2, Receptors, Chemokine - genetics, RNA, Messenger - genetics, RNA, Messenger - metabolism, Survival Rate, Th1 Cells - cytology, Th1 Cells - drug effects, Th1 Cells - immunology, Th1 Cells - metabolism, Thioglycolates - pharmacology, Tumor Necrosis Factor-alpha - pharmacology