miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3

Area of Science:

• Biochemistry
• Molecular Biology
• Cardiovascular Research

Background:

• Peripheral arterial disease (PAD) is a significant global health concern, ranking third in cardiovascular morbidity.
• MicroRNAs (miRs) are key regulators of gene expression, involved in various pathologies including cardiovascular diseases.
• The specific role of miR-124-3p in PAD pathogenesis remained largely unexplored.

Purpose of the Study:

• To investigate the role and mechanism of miR-124-3p in the development of peripheral arterial disease.
• To determine if miR-124-3p influences angiogenesis, a critical process in PAD.
• To explore miR-124-3p as a potential diagnostic or therapeutic target for PAD.

Main Methods:

• Quantitative reverse transcription PCR (RT-qPCR) to measure miR-124-3p expression in a hindlimb ischemia (HLI) model and hypoxic endothelial cells.
• In vitro assays (proliferation, wound healing, tube formation) to assess angiogenesis.
• In vivo HLI model to evaluate miR-124-3p function in angiogenesis.
• Dual-luciferase reporter assay to identify miR-124-3p targets.
• Correlation analysis between blood miR-124-3p levels and ankle-brachial index (ABI) in patients.

Main Results:

• miR-124-3p expression was significantly upregulated in ischemic tissues of the HLI model and hypoxic endothelial cells.
• miR-124-3p demonstrated inhibitory effects on angiogenesis both in vitro and in vivo.
• STAT3 was identified as a direct target of miR-124-3p.
• Blood levels of miR-124-3p showed a negative correlation with the ankle-brachial index, indicating its association with PAD severity.

Conclusions:

• miR-124-3p acts as a critical regulator that inhibits angiogenesis in the context of PAD.
• miR-124-3p presents potential as a diagnostic biomarker and a therapeutic target for peripheral arterial disease.