FoxO3a regulated by miR-150-5p promotes the pyroptosis of macrophages in atherosclerosis

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Exosome Biology

Background:

• Atherosclerosis (AS) pathogenesis involves complex molecular mechanisms.
• The role of exosomal microRNA-150-5p (miR-150-5p) in AS is not fully understood.
• Investigating exosomal miR-150-5p offers insights into AS pathophysiology.

Purpose of the Study:

• To elucidate the role of exosomal miR-150-5p in atherosclerosis.
• To identify downstream targets of miR-150-5p in AS.
• To evaluate the therapeutic potential of miR-150-5p inhibitors in AS.

Main Methods:

• Exosome isolation and analysis from AS mouse vascular tissue.
• Dual luciferase assays for miRNA-target validation.
• RT-qPCR, Western blot, and in vivo studies (HE, Masson, immunofluorescence) to assess gene expression and therapeutic efficacy.

Main Results:

• Exosomal miR-150-5p levels were elevated in AS, correlating with decreased FoxO3a expression.
• miR-150-5p promotes macrophage pyroptosis by targeting FoxO3a.
• miR-150-5p inhibition attenuated ox-LDL-induced cellular injury and pyroptosis in vitro and suppressed AS progression in vivo.

Conclusions:

• Exosomal miR-150-5p plays a significant role in promoting pyroptosis in atherosclerosis.
• Targeting miR-150-5p with inhibitors presents a promising therapeutic strategy for AS.
• This study enhances understanding of molecular mechanisms underlying AS progression.