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Subject | Predicate | Object |
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http://purl.uniprot.org/citations/26584135 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/26584135 | http://www.w3.org/2000/01/rdf-schema#comment | "Background and aimsMonoglyceride lipase (MGL) catalyzes the final step of lipolysis by degrading monoglyceride (MG) to glycerol and fatty acid. MGL also hydrolyzes and thereby deactivates 2-arachidonoyl glycerol (2-AG), the most abundant endocannabinoid in the mammalian system. 2-AG acts as full agonist on cannabinoid receptor type 1 (CB1R) and CB2R, which are mainly expressed in brain and immune cells, respectively. Thus, we speculated that in the absence of MGL, increased 2-AG concentrations mediate CB2R signaling in immune cells to modulate inflammatory responses, thereby affecting the development of atherosclerosis.Methods and resultsWe generated apolipoprotein E (ApoE)/MGL double-knockout (DKO) mice and challenged them with Western-type diet for 9 weeks. Despite systemically increased 2-AG concentrations in DKO mice, CB2R-mediated signaling remains fully functional, arguing against CB2R desensitization. We found increased plaque formation in both en face aortae (1.3-fold, p = 0.028) and aortic valve sections (1.5-fold, p = 0.0010) in DKO mice. Interestingly, DKO mice also presented reduced lipid (12%, p = 0.031) and macrophage content (18%, p = 0.061), elevated intraplaque smooth muscle staining (1.4-fold, p = 0.016) and thicker fibrous caps (1.8-fold, p = 0.0032), together with a higher ratio of collagen to necrotic core area (2.5-fold, p = 0.0003) and expanded collagen content (1.6-fold, p = 0.0007), which suggest formation of less vulnerable atherosclerotic plaques. Treatment with a CB2R inverse agonist prevents these effects in DKO mice, demonstrating that the observed plaque phenotype in DKO mice originates from CB2R activation.ConclusionLoss of MGL modulates endocannabinoid signaling in CB2R-expressing cells, which concomitantly affects the pathogenesis of atherosclerosis. We conclude that despite larger lesion size loss of MGL improves atherosclerotic plaque stability. Thus, pharmacological MGL inhibition may be a novel intervention to reduce plaque rupture."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.atherosclerosis.2015.10.109"xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Zimmermann R."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Eichmann T.O."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Goeritzer M."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Kratky D."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Lass A."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Hoefler G."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Schauer S."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Graier W.F."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Madreiter-Sokolowski C.T."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Schlager S."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Rainer S."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Rosenberger A."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Radovic B."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Doddapattar P."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Vujic N."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/author | "Woelfler A."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/name | "Atherosclerosis"xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/pages | "9-21"xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/title | "Monoglyceride lipase deficiency modulates endocannabinoid signaling and improves plaque stability in ApoE-knockout mice."xsd:string |
http://purl.uniprot.org/citations/26584135 | http://purl.uniprot.org/core/volume | "244"xsd:string |
http://purl.uniprot.org/citations/26584135 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26584135 |