miR-448-3p controls intracranial aneurysm by regulating KLF5 expression

Area of Science:

• Vascular Biology
• Molecular Medicine
• Genetics

Background:

• MicroRNAs (miRNAs) regulate cellular processes implicated in aneurysm development.
• Intracranial aneurysms (IAs) are complex vascular diseases with limited treatment options.

Purpose of the Study:

• To investigate the role of miR-448-3p in the progression of intracranial aneurysms.
• To identify the molecular targets and mechanisms underlying miR-448-3p's function in IA.

Main Methods:

• Surgically induced intracranial aneurysms in Sprague-Dawley rats.
• Quantified miR-448-3p and KLF5 expression levels in aneurysm tissues.
• Utilized cell culture models (SMCs and RAW 264.7 macrophages) to validate molecular targets and inflammatory responses.
• Assessed aneurysm size, wall thickness, and macrophage infiltration post-treatment.

Main Results:

• miR-448-3p was significantly downregulated, while KLF5 was upregulated in IA rat models.
• Klf5 was identified as a direct target of miR-448-3p in smooth muscle cells.
• miR-448-3p treatment reduced aneurysm size, lumen area, and protected wall thickness.
• miR-448-3p suppressed macrophage infiltration and KLF5, MMP2, and MMP9 expression in response to LPS stimulation.

Conclusions:

• miR-448-3p acts as a crucial inhibitor of intracranial aneurysm progression.
• Overexpression of miR-448-3p prevents IA development by downregulating KLF5 and suppressing macrophage-mediated inflammation.