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Regulation and possible role of endocannabinoids and related mediators in hypercholesterolemic mice with atherosclerosis.
- Source :
-
Atherosclerosis [Atherosclerosis] 2009 Aug; Vol. 205 (2), pp. 433-41. Date of Electronic Publication: 2009 Jan 09. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Amides
Animals
Aorta metabolism
Apolipoproteins E genetics
Atherosclerosis metabolism
Camphanes pharmacology
Cholesterol metabolism
Ethanolamines
Hypercholesterolemia metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Oleic Acids metabolism
Palmitic Acids metabolism
Pyrazoles pharmacology
Receptor, Cannabinoid, CB2 metabolism
Atherosclerosis genetics
Cannabinoid Receptor Modulators metabolism
Endocannabinoids
Hypercholesterolemia genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1484
- Volume :
- 205
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 19187936
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2008.12.040