TY - JOUR
T1 - Cannabinoid CB1 receptor inhibition decreases vascular smooth muscle migration and proliferation
AU - Rajesh, Mohanraj
AU - Mukhopadhyay, Partha
AU - Haskó, György
AU - Pacher, Pál
N1 - Funding Information:
This publication was supported by Intramural Research Program of NIH. The authors declare no conflicting financial interests.
PY - 2008/12/26
Y1 - 2008/12/26
N2 - Vascular smooth muscle proliferation and migration triggered by inflammatory stimuli and chemoattractants such as platelet-derived growth factor (PDGF) are key events in the development and progression of atherosclerosis and restenosis. Cannabinoids may modulate cell proliferation and migration in various cell types through cannabinoid receptors. Here we investigated the effects of CB1 receptor antagonist rimonabant (SR141716A), which has recently been shown to have anti-atherosclerotic effects both in mice and humans, on PDGF-induced proliferation, migration, and signal transduction of human coronary artery smooth muscle cells (HCASMCs). PDGF induced Ras and ERK 1/2 activation, while increasing proliferation and migration of HCASMCs, which were dose dependently attenuated by CB1 antagonist, rimonabant. These findings suggest that in addition to improving plasma lipid alterations and decreasing inflammatory cell migration and inflammatory response, CB1 antagonists may exert beneficial effects in atherosclerosis and restenosis by decreasing vascular smooth muscle proliferation and migration.
AB - Vascular smooth muscle proliferation and migration triggered by inflammatory stimuli and chemoattractants such as platelet-derived growth factor (PDGF) are key events in the development and progression of atherosclerosis and restenosis. Cannabinoids may modulate cell proliferation and migration in various cell types through cannabinoid receptors. Here we investigated the effects of CB1 receptor antagonist rimonabant (SR141716A), which has recently been shown to have anti-atherosclerotic effects both in mice and humans, on PDGF-induced proliferation, migration, and signal transduction of human coronary artery smooth muscle cells (HCASMCs). PDGF induced Ras and ERK 1/2 activation, while increasing proliferation and migration of HCASMCs, which were dose dependently attenuated by CB1 antagonist, rimonabant. These findings suggest that in addition to improving plasma lipid alterations and decreasing inflammatory cell migration and inflammatory response, CB1 antagonists may exert beneficial effects in atherosclerosis and restenosis by decreasing vascular smooth muscle proliferation and migration.
KW - Atherosclerosis
KW - Cannabinoid receptors
KW - Endocannabinoids
KW - Migration
KW - Proliferation
KW - Restenosis
KW - Rimonabant
KW - Vascular smooth muscle
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U2 - 10.1016/j.bbrc.2008.10.159
DO - 10.1016/j.bbrc.2008.10.159
M3 - Article
C2 - 18996082
AN - SCOPUS:56349095425
SN - 0006-291X
VL - 377
SP - 1248
EP - 1252
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -