Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

“…Given that substrates such as PEA are produced on demand, rather than being constitutive, enzymes like NAAA are probably intended to modulate their availability. In some instances, blocking FAAH is reported to actually result in paradoxical effects [72,73]. This may be a consequence of the fact that, in order to exert a regulatory effect on non-neuronal cells (e.g., glia and mast cells) implicated in neuroinflammation, PEA pleiotropic effects [74] should thus be tightly controlled by a mechanism allowing for inactivation.…”

Oxyradical Stress, Endocannabinoids, and Atherosclerosis

“…For example, JWH-133, a CB 2 agonist, reduced O 2 ·− generation, increased ERK 1/2 and STAT3 phosphorylation, inhibited chemotaxis, and increased the expression of CR3 on inflammatory cells [ 34 ]. On the other hand, when ApoE −/− mice on a high-cholesterol diet were simultaneously treated with the FAAH inhibitor URB597, the level of matrix metaloproteinase-9 increased in the lesion, the vascular collagen content decreased, and plaque vulnerability increased as compared with control vehicle-treated ApoE −/− mice on the same diet [ 56 ]. This result suggested that an increased eCB concentration (in this case AEA) in the vessel wall might have negative effects on disease progression.…”

Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice

“…The two best-studied endocannabinoids are N-arachidonoylethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), the latter being synthesised by diacylglycerol lipase (DAGL) and degraded by monoacylglycerol lipase (MAGL; [ 12 ]). While the relevance of AEA and its regulating enzymes to atherogenesis has already been demonstrated before [ 6 ; 13 ], the significance of 2-AG to the formation of atherosclerosis is less well established. Montecucco and coworkers have already described elevated 2-AG levels in the aortas of ApoE-deficient mice following a high cholesterol diet [ 14 ].…”