201. Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice
- Author
-
Benedikt Schöne, P Pfeifer, Andreas Zimmer, Katharina Schild, Friedrich Felix Hoyer, Laura Bindila, Dieter Lütjohann, Julian Jehle, Imke Jenniches, Georg Nickenig, and Beat Lutz
- Subjects
0301 basic medicine ,Apolipoprotein E ,medicine.medical_specialty ,Myeloid ,Diacylglycerol lipase ,lcsh:Medicine ,Inflammation ,Blood Pressure ,030204 cardiovascular system & hematology ,Receptor, Cannabinoid, CB2 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Apolipoproteins E ,Heart Rate ,Superoxides ,Internal medicine ,medicine ,Animals ,Myeloid Cells ,lcsh:Science ,Receptor ,Vascular tissue ,Mice, Knockout ,Lipoprotein lipase ,Multidisciplinary ,biology ,Macrophages ,lcsh:R ,Atherosclerosis ,Endocannabinoid system ,Plaque, Atherosclerotic ,Lipoprotein Lipase ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Biochemistry ,biology.protein ,lcsh:Q ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Research Article - Abstract
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 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. 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. more...
- Published
- 2016