Lysophosphatidylglucoside/GPR55 signaling promotes foam cell formation in human M2c macrophages

Area of Science:

• Cardiovascular Biology
• Cellular Metabolism
• Molecular Signaling

Background:

• Atherosclerosis, a leading cause of cardiovascular disease, involves intravascular plaques with necrotic cores.
• Macrophages within plaques play crucial roles, but excessive lipid uptake leads to foam cell formation and disease progression.
• G-protein-coupled receptor 55 (GPR55) signaling is implicated in atherosclerosis, yet its physiological ligands and specific roles are not fully understood.

Purpose of the Study:

• To investigate the role of lysophosphatidylglucoside (lysoPtdGlc)/GPR55 signaling in macrophage foam cell formation.
• To determine if lysoPtdGlc, a specific GPR55 ligand, influences cholesterol homeostasis and lipid accumulation in macrophages.

Main Methods:

• Utilized monocyte-derived M2c macrophages to study lysoPtdGlc/GPR55 signaling.
• Assessed the impact of lysoPtdGlc/GPR55 signaling on ATP binding cassette subfamily A member 1 (ABCA1) translocation and cholesterol efflux.
• Employed a GPR55 antagonist (ML193) to evaluate the specificity of the observed effects.

Main Results:

• LysoPtdGlc/GPR55 signaling in M2c macrophages inhibited ABCA1 translocation to the plasma membrane.
• This signaling pathway suppressed cholesterol efflux from macrophages.
• The inhibitory effects on cholesterol efflux and ABCA1 translocation were reversed by the GPR55 antagonist ML193, indicating pathway specificity.
• LysoPtdGlc/GPR55 signaling contributed to excessive lipid accumulation, promoting foam cell formation.

Conclusions:

• Lysophosphatidylglucoside (lysoPtdGlc) and G-protein-coupled receptor 55 (GPR55) signaling are involved in promoting foam cell formation.
• This signaling pathway negatively regulates cholesterol efflux in M2c macrophages.
• The lysoPtdGlc/GPR55 axis represents a potential therapeutic target for mitigating atherosclerosis progression.