Resolvin D2 limits atherosclerosis progression via myeloid cell-GPR18.

Autor: Lipscomb M; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA., Walis S; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA., Marinello M; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA., Mena HA; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., MacNamara KC; The Department of Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA., Spite M; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Fredman G; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Mar 31; Vol. 38 (6), pp. e23555.
DOI: 10.1096/fj.202302336RR
Abstrakt: 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/fl➔Ldlr -/- 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/fl➔Ldlr -/- mice, but not in the mKO➔Ldlr -/- 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.
(© 2024 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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