PMID- 38498346
OWN - NLM
STAT- MEDLINE
DCOM- 20240320
LR  - 20240412
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 38
IP  - 6
DP  - 2024 Mar 31
TI  - Resolvin D2 limits atherosclerosis progression via myeloid cell-GPR18.
PG  - e23555
LID - 10.1096/fj.202302336RR [doi]
AB  - 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.
CI  - (c) 2024 Federation of American Societies for Experimental Biology.
FAU - Lipscomb, Masharh
AU  - Lipscomb M
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Walis, Sean
AU  - Walis S
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Marinello, Michael
AU  - Marinello M
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Mena, Hebe Agustina
AU  - Mena HA
AD  - 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.
FAU - MacNamara, Katherine C
AU  - MacNamara KC
AUID- ORCID: 0000-0001-6202-4700
AD  - The Department of Immunology and Microbial Disease, Albany Medical College, 
      Albany, New York, USA.
FAU - Spite, Matthew
AU  - Spite M
AUID- ORCID: 0000-0002-8868-3648
AD  - 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.
FAU - Fredman, Gabrielle
AU  - Fredman G
AUID- ORCID: 0000-0001-9974-0962
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
LA  - eng
GR  - R01 HL153019/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (resolvin D2)
RN  - EC 3.5.3.1 (Arginase)
RN  - EC 3.4.22.- (Caspase 3)
RN  - 0 (GPR18 protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 25167-62-8 (Docosahexaenoic Acids)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Arginase
MH  - Caspase 3
MH  - Macrophages
MH  - Inflammation
MH  - *Atherosclerosis/genetics
MH  - Necrosis
MH  - Receptors, G-Protein-Coupled/genetics
MH  - *Docosahexaenoic Acids
OTO - NOTNLM
OT  - atherosclerosis
OT  - inflammation
OT  - macrophage
OT  - myeloid
OT  - resolution
OT  - resolvin
EDAT- 2024/03/19 00:42
MHDA- 2024/03/20 06:44
CRDT- 2024/03/18 12:52
PHST- 2024/02/21 00:00 [revised]
PHST- 2023/11/13 00:00 [received]
PHST- 2024/02/28 00:00 [accepted]
PHST- 2024/03/20 06:44 [medline]
PHST- 2024/03/19 00:42 [pubmed]
PHST- 2024/03/18 12:52 [entrez]
AID - 10.1096/fj.202302336RR [doi]
PST - ppublish
SO  - FASEB J. 2024 Mar 31;38(6):e23555. doi: 10.1096/fj.202302336RR.