Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice.
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 marro...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4712127?pdf=render |
id |
doaj-bd81e1fbe15b4f5397ed63f86dee160c |
---|---|
record_format |
Article |
spelling |
doaj-bd81e1fbe15b4f5397ed63f86dee160c2020-11-25T00:24:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014626710.1371/journal.pone.0146267Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice.Julian JehleFriedrich Felix HoyerBenedikt SchönePhilipp PfeiferKatharina SchildImke JennichesLaura BindilaBeat LutzDieter LütjohannAndreas ZimmerGeorg NickenigBACKGROUND: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.http://europepmc.org/articles/PMC4712127?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julian Jehle Friedrich Felix Hoyer Benedikt Schöne Philipp Pfeifer Katharina Schild Imke Jenniches Laura Bindila Beat Lutz Dieter Lütjohann Andreas Zimmer Georg Nickenig |
spellingShingle |
Julian Jehle Friedrich Felix Hoyer Benedikt Schöne Philipp Pfeifer Katharina Schild Imke Jenniches Laura Bindila Beat Lutz Dieter Lütjohann Andreas Zimmer Georg Nickenig Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice. PLoS ONE |
author_facet |
Julian Jehle Friedrich Felix Hoyer Benedikt Schöne Philipp Pfeifer Katharina Schild Imke Jenniches Laura Bindila Beat Lutz Dieter Lütjohann Andreas Zimmer Georg Nickenig |
author_sort |
Julian Jehle |
title |
Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice. |
title_short |
Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice. |
title_full |
Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice. |
title_fullStr |
Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice. |
title_full_unstemmed |
Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice. |
title_sort |
myeloid-specific deletion of diacylglycerol lipase α inhibits atherogenesis in apoe-deficient mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4712127?pdf=render |
work_keys_str_mv |
AT julianjehle myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT friedrichfelixhoyer myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT benediktschone myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT philipppfeifer myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT katharinaschild myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT imkejenniches myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT laurabindila myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT beatlutz myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT dieterlutjohann myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT andreaszimmer myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice AT georgnickenig myeloidspecificdeletionofdiacylglycerollipaseainhibitsatherogenesisinapoedeficientmice |
_version_ |
1725352564171472896 |