Article de Périodique
Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice (2005)
(Un traitement à base de faible dose orale de cannabinoïdes réduit la progression de l'artériosclérose chez la souris.)
Auteur(s) :
STEFFENS, S. ;
VEILLARD, N. R. ;
ARNAUD, C. ;
PELLI G. ;
BURGER, F. ;
STAUB, C. ;
ZIMMER, A. ;
FROSSARD J. L. ;
MACH F.
Année :
2005
Page(s) :
782-786
Langue(s) :
Anglais
Refs biblio. :
30
Domaine :
Drogues illicites / Illicit drugs
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Résumé :
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-{PRIVATE}{PRIVATE "TYPE=PICT;ALT=gamma"} secretion. Macrophage chemotaxis, which is a crucial step for the development of atherosclerosis1, 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.
Affiliation :
Division of Cardiology, Department of Medicine, Foundation for Medical Research, University Hospital, Faculty of Medicine, Geneva, Switzerland