MicroRNA deregulation in symptomatic carotid plaque

Area of Science:

• Cardiovascular Biology
• Molecular Genetics
• Stroke Pathophysiology

Background:

• Carotid artery stenosis is a major cause of stroke, with plaque embolization being a direct cause in 20% of cases.
• The genetic underpinnings of carotid plaque destabilization and rupture, particularly the role of microRNAs (miRNAs), remain largely unexplored.
• Understanding miRNA involvement could reveal novel mechanisms contributing to stroke.

Purpose of the Study:

• To compare the expression levels of seven specific microRNAs (miR-100, miR-125a, miR-127, miR-133a, miR-145, miR-155, and miR-221) in symptomatic versus asymptomatic human carotid plaques.
• To investigate the potential role of these miRNAs in carotid plaque progression and instability.
• To identify potential miRNA biomarkers for stroke risk associated with carotid stenosis.

Main Methods:

• Prospective inclusion of 30 patients undergoing carotid endarterectomy.
• Classification of carotid plaques into symptomatic (n=15) and asymptomatic (n=15) groups based on stroke history.
• Quantification of microRNA expression using real-time polymerase chain reaction (RT-PCR) on isolated RNA from plaque tissue.

Main Results:

• Patient groups were comparable regarding age, gender, risk factors, medication, and stenosis severity.
• Six of the seven investigated miRNAs (miR-100, miR-125a, miR-127, miR-133a, miR-145, and miR-221) were significantly overexpressed in symptomatic plaques compared to asymptomatic ones.
• miR-125a expression showed a significant inverse correlation with low-density lipoprotein cholesterol levels in the symptomatic group.

Conclusions:

• This pilot study suggests a potential regulatory role for specific miRNAs in the development of unstable carotid plaques, increasing stroke risk.
• The findings highlight miR-100, miR-125a, miR-127, miR-133a, miR-145, and miR-221 as potential contributors to plaque instability and rupture.
• Larger studies are warranted to validate these miRNAs as potential biomarkers or therapeutic targets for stroke prevention and treatment.