Chemokine binding protein 'M3' limits atherosclerosis in apolipoprotein E-/- mice

Area of Science:

• Cardiovascular Research
• Immunology
• Molecular Biology

Background:

• Chemokines play a crucial role in macrophage recruitment and the progression of atherosclerosis.
• The chemokine binding protein M3 inactivates key chemokines implicated in atherosclerosis, such as CCL2, CCL5, and CX3CL1.

Purpose of the Study:

• To investigate the impact of M3 on the development and composition of atherosclerotic plaques.
• To evaluate the efficacy of M3 in modulating chemokine activity and monocyte migration in vitro and in vivo.

Main Methods:

• In vitro chemotaxis assays using human monocytes and chemokines CCL2, CCL5, and CX3CL1.
• In vivo studies using apolipoprotein (apo)-E-/- mice in 'rapid promotion' (high-fat diet) and 'slow progression' (chow diet) atherosclerosis models.
• Systemic infusion of adenoviruses encoding M3 (AdM3) or green fluorescence protein (AdGFP) as a control.

Main Results:

• AdM3 infusion suppressed plasma chemokine activity and ex vivo monocyte migration.
• In the 'slow progression' model, AdM3 mice showed reduced lesion area and increased smooth muscle cell α-actin expression.
• In the 'rapid promotion' model, AdM3 mice exhibited reduced plaque macrophage content, suppressed lipid deposition, and decreased phosphorylated p65 (NF-κb).
• M3 inhibited liver CCL2 concentrations, but not CCL5 or systemic chemokine levels.

Conclusions:

• M3 demonstrates varying effects on atherosclerosis progression and plaque composition, dependent on the rate of lesion development.
• Chemokine inhibition via M3 presents a promising therapeutic strategy for atherosclerosis treatment.
• M3 effectively reduces key inflammatory markers and cellular infiltration in atherosclerotic lesions.