MicroRNA-145 targeted therapy reduces atherosclerosis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Gene Therapy

Background:

• MicroRNAs are key regulators of gene expression involved in chronic diseases.
• MicroRNA-145 (miR-145) is highly expressed in vascular smooth muscle cells (VSMCs) and influences their fate.
• The role of miR-145 in atherosclerosis and plaque stability requires further investigation.

Purpose of the Study:

• To investigate the therapeutic potential of microRNA-145 (miR-145) in modulating atherosclerosis.
• To determine if VSMC-specific overexpression of miR-145 impacts atherosclerotic plaque development and stability in vivo.

Main Methods:

• Apolipoprotein E knockout (ApoE(-/-)) mice were treated with a lentivirus expressing miR-145 under a VSMC-specific promoter (SM22α) or a control lentivirus.
• Mice were fed a Western diet for 12 weeks to induce atherosclerosis.
• Atherosclerotic lesions were analyzed for plaque size, morphology, cellular composition, and VSMC phenotype markers.

Main Results:

• SMC-targeted miR-145 delivery significantly reduced atherosclerotic plaque size in major arteries.
• Treatment increased fibrous cap area, collagen content, and VSMC markers (calponin, α-smooth muscle actin), while decreasing necrotic core area and macrophage infiltration.
• miR-145 overexpression reduced KLF4 and increased myocardin expression, promoting a contractile VSMC phenotype.

Conclusions:

• VSMC-specific overexpression of miR-145 is a novel therapeutic strategy to limit atherosclerotic plaque progression.
• This approach effectively modifies plaque morphology and cellular composition, enhancing stability and reducing rupture risk.
• miR-145 holds promise as a target for treating atherosclerosis and preventing plaque rupture.