Myeloid-Specific Deletion of XXXX Lipase a Inhibits Atherogenesis in @entity6970 -Deficient @entity19 .

@entity32 @entity2366 @entity14512 @entity6970 @entity9394 @entity19 @entity14651 @entity10062 @entity72652 @entity731 @entity165
BACKGROUND: The endocannabinoid @entity9394 ( @entity14512 ) is a known modulator of @entity32 . Despite its high concentration in vascular tissue, the role of @entity14512 in atherogenesis has not yet been examined. METHODS: @entity6970 -deficient @entity19 were sublethally irradiated and reconstituted with bone marrow from @entity19 with a myeloid-specific knockout of the @entity14512 synthesising enzyme @entity2366 lipase a ( @entity72652 ) or control bone marrow with an intact @entity14512 biosynthesis. After a @entity165 -rich diet for 8 weeks, plaque size and plaque morphology were examined in chimeric @entity19 . Circulating inflammatory cells were assessed by flow cytometry. Aortic tissue and plasma levels of endocannabinoids were measured using liquid chromatography-multiple reaction monitoring. RESULTS: @entity19 with @entity72652 -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 @entity731 of @entity72652 -deficient @entity19 . Moreover, @entity14651 expression and the amount of oxidised LDL within @entity731 was significantly reduced. @entity10062 analyses revealed that levels of circulating inflammatory cells were unaltered in @entity72652 -deficient @entity19 . CONCLUSIONS: Myeloid synthesis of the endocannabinoid @entity14512 appears to promote @entity32 and atherogenesis. Thus, myeloid-specific disruption of @entity14512 synthesis may represent a potential novel therapeutic strategy against @entity731 .
