Oxygenized Low-Density Lipoprotein-Induced ASMC Dysregulation Depends on circ_0000345-Mediated Regulatory Mechanism

Area of Science:

• Molecular Biology
• Cardiovascular Research
• RNA Biology

Background:

• Vascular smooth muscle cells (ASMCs) are central to atherosclerosis development.
• Circular RNA hsa_circ_0000345 (circ_0000345) and miR-647 are implicated in oxidized low-density lipoprotein (ox-LDL)-induced ASMC dysfunction.
• The precise interaction between circ_0000345 and miR-647 in this context remains undefined.

Purpose of the Study:

• To elucidate the role and mechanism of circ_0000345 in ox-LDL-induced ASMC dysregulation.
• To investigate the regulatory relationship between circ_0000345, miR-647, and PAPD5 in the context of atherosclerosis.
• To determine if circ_0000345 can serve as a therapeutic target for atherosclerosis.

Main Methods:

• Quantitative real-time PCR (RT-qPCR) to measure circ_0000345, miR-647, and PAPD5 mRNA levels in patient serum and ASMCs.
• Gain-of-function experiments to assess the impact of circ_0000345 upregulation on ASMC proliferation, migration, invasion, and inflammation.
• Dual-luciferase reporter and RNA immunoprecipitation assays to validate molecular interactions.

Main Results:

• Circ_0000345 and PAPD5 were downregulated, while miR-647 was upregulated in atherosclerotic (AS) patient serum and ox-LDL-treated ASMCs.
• Circ_0000345 functions as a miR-647 sponge, and its upregulation inhibits ox-LDL-induced ASMC proliferation, migration, invasion, and inflammation.
• PAPD5 was identified as a direct target of miR-647, with circ_0000345 mediating PAPD5 expression by sequestering miR-647.

Conclusions:

• Circ_0000345 enhances PAPD5 expression by sponging miR-647, thereby alleviating ox-LDL-induced ASMC dysregulation.
• This circ_0000345/miR-647/PAPD5 axis plays a critical role in the pathogenesis of atherosclerosis.
• Circ_0000345 emerges as a significant factor in AS pathogenesis, suggesting potential therapeutic applications.