Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice.
Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice.
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DOI：
10.1371/journal.pone.0146267
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Nickenig G
中科院分区：
文献类型：
--
作者：
Jehle J;Hoyer FF;Schöne B;Pfeifer P;Schild K;Jenniches I;Bindila L;Lutz B;Lütjohann D;Zimmer A;Nickenig G
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. 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 α (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. 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. 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.
