Circular RNA as Therapeutic Targets in Atherosclerosis: Are We Running in Circles?

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Genetics

Background:

• Cardiovascular diseases, including atherosclerosis, involve complex genetic factors.
• Non-coding RNAs, such as circular RNAs (circRNAs) and micro-RNAs (miRNAs), are being investigated for their diagnostic and therapeutic potential in cardiovascular diseases.
• Assessing the risks, benefits, and long-term off-target effects of circRNA-based therapies is crucial.

Purpose of the Study:

• To review and analyze existing literature on circRNAs and atherosclerosis from 2016-2022.
• To investigate the mechanisms, expression patterns, and effects of circRNAs in the context of atherosclerosis.
• To identify and evaluate the consistency of findings regarding circRNA and miRNA manipulation in atherosclerosis models.

Main Methods:

• A systematic search of the PubMed database for publications on circRNA and atherosclerosis (2016-2022).
• Review of study designs, including atherosclerosis induction methods and their impact on circRNA expression.
• Analysis of investigated mechanisms, including miRNA interactions, gene targets, and effects on cellular mechanics and inflammatory markers.

Main Results:

• Observed numerous disparate, opposing, and contradictory findings across studies.
• Expression levels of specific circRNAs varied significantly in atherosclerotic environments.
• CircRNA or miRNA silencing demonstrated inconsistent effects on atherosclerosis progression, with notable off-target, cell-specific, and disease-specific effects.

Conclusions:

• The therapeutic targeting of circRNAs and miRNAs for cardiovascular diseases is complex due to inconsistent findings and variable expression.
• Significant potential for detrimental and unpredictable off-target effects exists.
• Current understanding suggests that therapeutic manipulation of circRNA or miRNA molecules in atherosclerosis may be complicated and perilous.