The resolvin D2 - GPR18 axis is expressed in human coronary atherosclerosis and transduces atheroprotection in apolipoprotein E deficient mice.
Biochem Pharmacol
; 201: 115075, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35525326
ABSTRACT
Chronic inflammation in atherosclerosis reflects a failure in the resolution of inflammation. Pro-resolving lipid mediators derived from omega-3 fatty acids reduce the development of atherosclerosis in murine models. The aim of the present study was to decipher the role of the specialized proresolving mediator (SPM) resolvin D2 (RvD2) in atherosclerosis and its signaling through the G-protein coupled receptor (GPR) 18. The ligand and receptor were detected in human coronary arteries in relation to the presence of atherosclerotic lesions and its cellular components. Importantly, RvD2 levels were significantly higher in atherosclerotic compared with healthy human coronary arteries. Furthermore, apolipoprotein E (ApoE) deficient hyperlipidemic mice were treated with either RvD2 or vehicle in the absence and presence of the GPR18 antagonist O-1918. RvD2 significantly reduced atherosclerosis, necrotic core area, and pro-inflammatory macrophage marker expression. RvD2 in addition enhanced macrophage phagocytosis. The beneficial effects of RvD2 were not observed in the presence of O-1918. Taken together, these results provide evidence of atheroprotective pro-resolving signalling through the RvD2-GPR18 axis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Doença da Artéria Coronariana
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Ácidos Docosa-Hexaenoicos
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Receptores Acoplados a Proteínas G
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Aterosclerose
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article