Circular RNAs in Cardiovascular Disease: Mechanisms, Biomarkers, and Therapeutic Frontiers

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Biomarker Discovery

Background:

• Circular RNAs (circRNAs) are key regulators of cardiovascular function through gene expression, microRNA sponging, and protein interactions.
• Their stable, covalently closed structure enables detection in blood and tissues, suggesting biomarker potential.
• circRNAs influence endothelial function, smooth muscle cell phenotype, inflammation, and cardiomyocyte survival.

Purpose of the Study:

• To review current research on circRNAs in cardiovascular diseases (atherosclerosis, myocardial infarction, heart failure).
• To explore the roles of specific circRNAs in vascular compartments and disease pathogenesis.
• To discuss the translational potential of circRNAs for diagnostics and therapeutics.

Main Methods:

• Literature review of studies investigating circRNAs in cardiovascular diseases.
• Analysis of circRNA functions in endothelial cells, smooth muscle cells, macrophages, and cardiomyocytes.
• Identification of disease-associated and compartment-specific circRNAs.

Main Results:

• circRNAs regulate key cardiovascular processes including endothelial function, smooth muscle cell plasticity, inflammatory responses, and cardiomyocyte survival.
• Specific circRNAs like circANRIL and circHIPK3 are frequently disease-promoting, while others like circFOXO3 have context-dependent roles.
• Compartment-specific circRNAs (e.g., circGNAQ, circLRP6, circROBO2, circZNF609) act as regulators within distinct vascular cell types.

Conclusions:

• circRNAs hold significant promise as blood-based multimarker panels for precise cardiovascular disease diagnosis.
• Targeted modulation of pathogenic circRNA circuits offers a novel therapeutic strategy.
• Clinical translation necessitates advancements in cell-type targeting, delivery methods, and off-target effect mitigation.