LRG1 promotes atherosclerosis by inducing macrophage M1-like polarization

Area of Science:

• Immunology
• Cardiovascular Biology
• Molecular Medicine

Background:

• Atherosclerosis is a chronic inflammatory arterial disease driven by lipid accumulation in macrophages.
• The precise mechanisms of macrophage proinflammatory polarization in atherosclerosis remain unclear.
• Identifying novel molecular players is crucial for understanding and treating atherosclerosis.

Purpose of the Study:

• To investigate the role of leucine-rich alpha-2 glycoprotein 1 (LRG1) in macrophage polarization during atherosclerosis.
• To explore LRG1 as a potential biomarker and therapeutic target for coronary artery disease (CAD).

Main Methods:

• Quantification of LRG1 levels in atherosclerotic tissues and CAD patient serum.
• In vitro studies assessing LRG1's effect on macrophage polarization via ERK1/2 and JNK pathways.
• In vivo studies using LRG1 knockout and ApoE-deficient mice fed a high-fat diet.
• Evaluation of anti-LRG1 neutralizing antibody efficacy in vitro and in vivo.

Main Results:

• LRG1 levels are elevated in atherosclerotic lesions and serum from CAD patients.
• LRG1 promotes M1-like proinflammatory macrophage polarization by activating ERK1/2 and JNK signaling.
• LRG1 knockout mice exhibit delayed atherogenesis and reduced proinflammatory cytokines.
• Anti-LRG1 antibody treatment mitigates LRG1-induced polarization and shows therapeutic benefits in an atherosclerosis model.

Conclusions:

• LRG1 is a key mediator of macrophage-driven inflammation in atherosclerosis.
• LRG1 serves as a potential biomarker for CAD.
• Targeting LRG1 offers a promising therapeutic strategy for CAD by modulating macrophage inflammatory responses.