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

Authors

Jeffrey Triska
Christo Mathew
Yang Zhao
Yuqing E Chen
Yochai Birnbaum

Publication Date

7-2-2023

Journal

Journal of Clinical Medicine

DOI

10.3390/jcm12134446

PMID

37445481

PMCID

PMC10342353

PubMedCentral® Posted Date

7-2-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

circular RNA, micro RNA, atherosclerosis, cardiovascular disease, potential therapeutic treatments

Abstract

Much attention has been paid lately to harnessing the diagnostic and therapeutic potential of non-coding circular ribonucleic acids (circRNAs) and micro-RNAs (miRNAs) for the prevention and treatment of cardiovascular diseases. The genetic environment that contributes to atherosclerosis pathophysiology is immensely complex. Any potential therapeutic application of circRNAs must be assessed for risks, benefits, and off-target effects in both the short and long term. A search of the online PubMed database for publications related to circRNA and atherosclerosis from 2016 to 2022 was conducted. These studies were reviewed for their design, including methods for developing atherosclerosis and the effects of the corresponding atherosclerotic environment on circRNA expression. Investigated mechanisms were recorded, including associated miRNA, genes, and ultimate effects on cell mechanics, and inflammatory markers. The most investigated circRNAs were then further analyzed for redundant, disparate, and/or contradictory findings. Many disparate, opposing, and contradictory effects were observed across experiments. These include levels of the expression of a particular circRNA in atherosclerotic environments, attempted ascertainment of the in toto effects of circRNA or miRNA silencing on atherosclerosis progression, and off-target, cell-specific, and disease-specific effects. The high potential for detrimental and unpredictable off-target effects downstream of circRNA manipulation will likely render the practice of therapeutic targeting of circRNA or miRNA molecules not only complicated but perilous.

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