MicroRNA-26b-/- augments atherosclerosis, while mimic-loaded nanoparticles reduce atherogenesis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• MicroRNA Therapeutics

Background:

• MicroRNAs (miRs) are implicated in atherosclerosis pathogenesis.
• miR-26b is upregulated in human atherosclerotic plaques.
• The specific role and therapeutic potential of miR-26b in atherosclerosis require elucidation.

Purpose of the Study:

• To investigate the cell-specific effects of miR-26b on atherosclerosis development.
• To determine the therapeutic potential of miR-26b in preclinical models.

Main Methods:

• Utilized Apoe-/-Mir26b-/- and myeloid-specific knockout mice on a Western-type diet.
• Assessed atherosclerotic plaque size, phenotype, and macrophage function.
• Employed lipid nanoparticles (LNPs) for miR-26b mimic delivery in vitro and in vivo.

Main Results:

• Apoe-/-Mir26b-/- mice exhibited significantly increased atherosclerotic lesion size in the aortic arch.
• Loss of miR-26b in myeloid cells promoted a pro-inflammatory macrophage phenotype and altered plaque composition.
• miR-26b mimics delivered via LNPs rescued these pro-atherosclerotic effects and demonstrated therapeutic potential.

Conclusions:

• miR-26b plays a crucial atheroprotective role by reducing lesion formation, inflammation, and promoting collagen breakdown.
• miR-26b mimic-loaded LNPs represent a promising therapeutic strategy for atherosclerosis.