Resolvin D2 limits atherosclerosis progression via myeloid cell-GPR18.
FASEB J
; 38(6): e23555, 2024 Mar 31.
Article
em En
| MEDLINE
| ID: mdl-38498346
ABSTRACT
Dysregulated inflammation-resolution programs are associated with atherosclerosis progression. Resolvins, in part, mediate inflammation-resolution programs. Indeed, Resolvin D2 (RvD2) activates GPR18, a G-protein-coupled receptor, and limits plaque progression, though the cellular targets of RvD2 remain unknown. Here, we developed a humanized GPR18 floxed ("fl/fl") and a myeloid (Lysozyme M Cre) GPR18 knockout (mKO) mouse. We functionally validated this model by assessing efferocytosis in bone marrow-derived macrophages (BMDMs) and found that RvD2 enhanced efferocytosis in the fl/fl, but not in the mKO BMDMs. To understand the functions of RvD2-GPR18 in atherosclerosis, we performed a bone marrow transfer of fl/fl or mKO bone marrow into Ldlr-/- recipients. For these experiments, we treated each genotype with either Vehicle/PBS or RvD2 (25 ng/mouse, 3 times/week for 3 weeks). Myeloid loss of GPR18 resulted in significantly more necrosis, increased cleaved caspase-3+ cells and decreased percentage of Arginase-1+ -Mac2+ cells without a change in overall Mac2+ plaque macrophages, compared with fl/flâLdlr-/- transplanted mice. RvD2 treatment decreased plaque necrosis, the percent of cleaved caspase-3+ cells and increased the percent of Arginase-1+ -Mac2+ cells in fl/flâLdlr-/- mice, but not in the mKOâLdlr-/- transplanted mice. These results suggest that GPR18 plays a causal role in limiting atherosclerosis progression and that RvD2's ability to limit plaque necrosis is in part dependent on myeloid GRP18.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Arginase
/
Ácidos Docosa-Hexaenoicos
/
Aterosclerose
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos