Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice
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Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. / Steffens, Sabine; Veillard, Niels R; Arnaud, Claire; Pelli, Graziano; Burger, Fabienne; Staub, Christian; Karsak, Meliha; Zimmer, Andreas; Frossard, Jean-Louis; Mach, François.
In: NATURE, Vol. 434, No. 7034, 07.04.2005, p. 782-6.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice
AU - Steffens, Sabine
AU - Veillard, Niels R
AU - Arnaud, Claire
AU - Pelli, Graziano
AU - Burger, Fabienne
AU - Staub, Christian
AU - Karsak, Meliha
AU - Zimmer, Andreas
AU - Frossard, Jean-Louis
AU - Mach, François
PY - 2005/4/7
Y1 - 2005/4/7
N2 - 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-gamma 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.
AB - 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-gamma 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.
KW - Animals
KW - Apolipoproteins E/deficiency
KW - Arteriosclerosis/complications
KW - Cells, Cultured
KW - Chemotaxis, Leukocyte/drug effects
KW - Disease Models, Animal
KW - Disease Progression
KW - Dronabinol/administration & dosage
KW - Humans
KW - Inflammation/complications
KW - Interferon-gamma/metabolism
KW - Macrophages/cytology
KW - Mice
KW - Mice, Knockout
KW - RNA, Messenger/genetics
KW - Receptor, Cannabinoid, CB2/antagonists & inhibitors
KW - Receptors, CCR2
KW - Receptors, Chemokine/genetics
KW - Survival Rate
KW - Th1 Cells/cytology
KW - Thioglycolates/pharmacology
KW - Tumor Necrosis Factor-alpha/pharmacology
U2 - 10.1038/nature03389
DO - 10.1038/nature03389
M3 - SCORING: Journal article
C2 - 15815632
VL - 434
SP - 782
EP - 786
JO - NATURE
JF - NATURE
SN - 0028-0836
IS - 7034
ER -