Regulation and possible role of endocannabinoids and related mediators in hypercholesterolemic mice with atherosclerosis
Atherosclerosis. 2009-08-01; 205(2): 433-441
DOI: 10.1016/j.atherosclerosis.2008.12.040
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1. Atherosclerosis. 2009 Aug;205(2):433-41. doi:
10.1016/j.atherosclerosis.2008.12.040. Epub 2009 Jan 9.
Regulation and possible role of endocannabinoids and related mediators in
hypercholesterolemic mice with atherosclerosis.
Montecucco F(1), Matias I, Lenglet S, Petrosino S, Burger F, Pelli G,
Braunersreuther V, Mach F, Steffens S, Di Marzo V.
Author information:
(1)Department of Internal Medicine, University Hospital, Geneva, Switzerland.
In this study we analysed the possible modulation of endocannabinoids and
related molecules during atherosclerosis development in mice. Wild-type and
apolipoprotein E knockout (ApoE(-/-)) mice were fed either normal chow or
high-cholesterol diet for 8-12 weeks, and tissue endocannabinoid levels were
measured by liquid chromatography-mass spectrometry. We found increased levels
of 2-AG in aortas and visceral adipose tissue (VAT) of ApoE(-/-) mice fed on
high-cholesterol diet for 12 weeks as compared to ApoE(-/-) mice fed on normal
chow or wild-type mice fed on cholesterol. No significant difference in 2-AG
levels was observed after 8 weeks of diet, and no changes in anandamide levels
were found in any group. The levels of the anandamide-related mediators with
anti-inflammatory or anti-lipogenic properties, palmitoylethanolamide (PEA) and
oleoylethanolamide (OEA), decreased or increased only in VAT or in both tissues,
respectively. Endocannabinoid- and OEA/PEA-degrading enzymes were expressed by
macrophages within atherosclerotic lesions. In vitro, 2-AG and OEA-induced
monocyte migration at 0.3-1microM, which corresponds to the levels observed in
aortas. PEA 1microM also induced monocyte migration but counteracted the effect
of 2-AG, whereas OEA enhanced it. Enhanced 2-AG levels in advanced
atherosclerotic lesions may trigger the inflammatory process by recruiting more
inflammatory cells and inducing extracellular matrix degradation via CB(2)
receptors, and this possibility was supported in vitro but not in vivo by
experiments with the CB(2) antagonist, SR144528.
DOI: 10.1016/j.atherosclerosis.2008.12.040
PMID: 19187936 [Indexed for MEDLINE]