Synthetically designed circRNA can be used to target cardiovascular relevant microRNAs to improve cellular function.

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• RNA Therapeutics

Background:

• Vascular aging, endothelial dysfunction, and cellular senescence contribute to cardiovascular diseases (CVDs).
• MicroRNAs (miRNAs), specifically miR-21-5p and miR-146a-5p, play critical roles in CVD development by influencing inflammation, fibrosis, and cell proliferation.
• Circular RNAs (circRNAs) are emerging as stable inhibitors for miRNA-based therapeutics.

Purpose of the Study:

• To investigate the expression of miR-21-5p and miR-146a-5p in senescent vascular smooth muscle cells (VSMCs).
• To evaluate the efficacy of synthetic circRNAs in inhibiting these specific miRNAs within VSMCs.
• To assess the impact of circRNA-mediated miRNA inhibition on gene expression and cellular functions in senescent VSMCs.

Main Methods:

• Senescent human vascular smooth muscle cells (VSMCs) were transfected with custom-designed circRNAs targeting miR-21-5p and miR-146a-5p.
• Analysis of miRNA and target gene expression levels.
• Assessment of cellular functions including proliferation and migration.

Main Results:

• CircRNA-mediated inhibition of miR-21-5p and miR-146a-5p significantly altered gene expression in senescent VSMCs.
• The inhibition impacted cellular behaviors such as proliferation and migration.
• Synthetic circRNAs demonstrated effective inhibition of target miRNAs in VSMCs.

Conclusions:

• CircRNAs are effective and stable inhibitors of miR-21-5p and miR-146a-5p in senescent vascular cells.
• CircRNA-based miRNA inhibition presents a promising therapeutic strategy for vascular aging and associated cardiovascular diseases.
• This approach may offer advantages over traditional anti-miRs due to enhanced stability.