Resolvin D2 limits atherosclerosis progression via myeloid cell-GPR18

Area of Science:

• Immunology
• Cardiovascular Research
• Pharmacology

Background:

• Dysregulated inflammation resolution contributes to atherosclerosis.
• Resolvins, like Resolvin D2 (RvD2), are key mediators of inflammation resolution.
• RvD2 activates GPR18, a receptor implicated in limiting plaque progression, but its cellular targets are unknown.

Purpose of the Study:

• To investigate the role of GPR18 in atherosclerosis.
• To determine if RvD2's atheroprotective effects are mediated through myeloid GPR18.

Main Methods:

• Developed humanized GPR18 floxed (fl/fl) and myeloid-specific GPR18 knockout (mKO) mice.
• Assessed efferocytosis in bone marrow-derived macrophages (BMDMs).
• Performed bone marrow transplantation into Ldlr-/- recipients and treated with RvD2 or vehicle.

Main Results:

• RvD2 enhanced efferocytosis in fl/fl BMDMs, but not in mKO BMDMs.
• Myeloid GPR18 deficiency led to increased plaque necrosis and apoptosis, and reduced efferocytosis markers.
• RvD2 reduced plaque necrosis and apoptosis in fl/fl recipients but not in mKO recipients.

Conclusions:

• GPR18 in myeloid cells plays a critical role in limiting atherosclerosis progression.
• RvD2's atheroprotective effects, specifically reducing plaque necrosis, are partly dependent on myeloid GPR18.