miR-133b Downregulation Reduces Vulnerable Plaque Formation in Mice with AS through Inhibiting Macrophage Immune...

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Inflammation Research

Background:

• Atherosclerosis (AS) is a chronic inflammatory disease driven by lipid deposition and macrophage involvement.
• Macrophage accumulation and function are central to AS pathogenesis and vulnerable plaque development.

Purpose of the Study:

• To investigate the role of microRNA-133b (miR-133b) in AS-related vulnerable plaque formation and vascular remodeling.
• To explore the underlying mechanisms involving the Notch-signaling pathway and macrophage behavior.

Main Methods:

• Established AS mouse models with altered miR-133b expression or blocked Notch-signaling pathway.
• Evaluated macrophage proliferation, migration, and apoptosis.
• Assessed AS plaque area, macrophage, and vascular smooth muscle cell (VSMC) rates.

Main Results:

• miR-133b was upregulated in AS and potentially targets MAML1 to regulate the Notch-signaling pathway.
• Downregulating miR-133b or inhibiting Notch signaling reduced AS plaque area and macrophage infiltration while increasing VSMC presence.
• Inhibition of Notch signaling or miR-133b downregulation decreased macrophage viability and migration and increased apoptosis.

Conclusions:

• Downregulated miR-133b inhibits macrophage immune responses, attenuating vulnerable plaque formation and vascular remodeling in AS.
• The MAML1-mediated Notch-signaling pathway is a key mechanism through which miR-133b influences AS.
• miR-133b represents a potential therapeutic target for managing atherosclerosis.