NPY promotes macrophage migration by upregulating matrix metalloproteinase-8 expression

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Macrophage migration is implicated in obesity-related cardiovascular diseases.
• Matrix metalloproteinase-8 (MMP-8) facilitates macrophage migration by degrading the extracellular matrix (ECM).
• Neuropeptide Y (NPY) influences MMP expression, but its role in regulating MMP-8 in macrophages and subsequent neointima formation is unclear.

Purpose of the Study:

• To investigate the role of Neuropeptide Y (NPY) in regulating matrix metalloproteinase-8 (MMP-8) expression and macrophage migration.
• To determine the impact of NPY on neointima formation following vascular injury.

Main Methods:

• Utilized wild-type and NPY knockout mice fed a high-fat diet, subjected to carotid artery injury.
• Analyzed neointima formation, macrophage content, and MMP-8 expression in vivo.
• Treated Raw264.7 macrophage cells with NPY, Y1R antagonist, and ERK1/2 inhibitor in vitro to assess MMP-8 expression and migration.

Main Results:

• NPY knockout mice showed significantly reduced neointima formation, macrophage infiltration, and MMP-8 levels post-injury.
• NPY upregulated MMP-8 mRNA and protein expression in macrophages via the Y1 receptor and ERK1/2 pathway.
• NPY enhanced macrophage migration across type I collagen in vitro.

Conclusions:

• Neuropeptide Y (NPY) promotes macrophage migration and neointima formation by upregulating matrix metalloproteinase-8 (MMP-8) expression.
• The NPY/Y1R/ERK1/2/MMP-8 axis represents a novel mechanism contributing to vascular injury progression.
• Targeting NPY signaling may offer a therapeutic strategy for cardiovascular diseases associated with neointima formation.