Role of peripheral endocannabinoid system in atherosclerosis
Final Report Abstract
Endocannabinoids are arachidonic acid-derived lipid mediators, which bind to cannabinoid receptors CB1 and CB2. The major endocannabinoids are anandamide and 2- arachidonoylglycerol (2-AG). Circulating endocannabinoid levels are increased in atherosclerosis and metabolic disorders, which is related to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids. Emerging experimental evidence suggests that enhanced endocannabinoid signaling affects atherosclerosis via multiple effects, including a modulation of vascular inflammation, leukocyte recruitment, macrophage cholesterol metabolism, and consequently atherosclerotic plaque stability. Despite some controversy in pro- or anti-inflammatory effects of inhibiting selective enzyme pathways of endocannabinoid metabolism, there is overwhelming evidence for a pathophysiological role of excessive CB1 activation by endocannabinoids in atherosclerosis and related metabolic complications. Thus, blocking CB1 signaling in the vasculature and peripheral organs might represent a promising therapeutic target in atherosclerosis. In view of a possible therapeutic application of peripherally active CB1 antagonists, we aim to further clarify cell-specific effects of vascular and hematopoietic CB1 in atherosclerosis.
Publications
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(2018). Cardiovascular effects of endocannabinoids, marijuana and synthetic cannabinoids: the good, the bad and the ugly. Nat Rev Cardiol 15(3):151-166
Pacher P, Steffens S, Hasko G, Schindler T, Kunos G
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(2018). Palmitoylethanolamide Promotes a Proresolving Macrophage Phenotype and Attenuates Atherosclerotic Plaque Formation. Arteriosclerosis, Thrombosis and Vascular Biology. Nov;38(11):2562-2575
Rinne P, Guillamat-Prats R, Rami M, Bindila L, Ring L, Lyytikäinen LP, Raitoharju E, Oksala N, Lehtimäki T, Weber C, van der Vorst EPC, Steffens S
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(2019). Deficiency of monoacylglycerol lipase enhances IgM plasma levels and limits atherogenesis in a CB2-dependent manner. Thrombosis Haemostasis 119(2):348-351
Guillamat-Prats R, Rami M, Ring L, Rinne P, Lauer E, Lenglet S, Thomas A, Pagano S, Vuilleumier N, Caravatt BF, Weber C, Faussner A, Steffens S
