| First Author | Jehle J | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 1 | Pages | e0146267 |
| PubMed ID | 26731274 | Mgi Jnum | J:249794 |
| Mgi Id | MGI:6093044 | Doi | 10.1371/journal.pone.0146267 |
| Citation | Jehle J, et al. (2016) Myeloid-Specific Deletion of Diacylglycerol Lipase alpha Inhibits Atherogenesis in ApoE-Deficient Mice. PLoS One 11(1):e0146267 |
| abstractText | BACKGROUND: The endocannabinoid 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation. Despite its high concentration in vascular tissue, the role of 2-AG in atherogenesis has not yet been examined. METHODS: ApoE-deficient mice were sublethally irradiated and reconstituted with bone marrow from mice with a myeloid-specific knockout of the 2-AG synthesising enzyme diacylglycerol lipase alpha (Dagla) or control bone marrow with an intact 2-AG biosynthesis. After a cholesterol-rich diet for 8 weeks, plaque size and plaque morphology were examined in chimeric mice. Circulating inflammatory cells were assessed by flow cytometry. Aortic tissue and plasma levels of endocannabinoids were measured using liquid chromatography-multiple reaction monitoring. RESULTS: Mice with Dagla-deficient bone marrow and circulating myeloid cells showed a significantly reduced plaque burden compared to controls. The reduction in plaque size was accompanied by a significantly diminished accumulation of both neutrophil granulocytes and macrophages in atherosclerotic lesions of Dagla-deficient mice. Moreover, CB2 expression and the amount of oxidised LDL within atherosclerotic lesions was significantly reduced. FACS analyses revealed that levels of circulating inflammatory cells were unaltered in Dagla-deficient mice. CONCLUSIONS: Myeloid synthesis of the endocannabinoid 2-AG appears to promote vascular inflammation and atherogenesis. Thus, myeloid-specific disruption of 2-AG synthesis may represent a potential novel therapeutic strategy against atherosclerosis. |
