Circular RNAs and endothelial dysfunction: mechanistic crosstalk and emerging therapeutic perspectives

Figures

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  Fig. 1. Biogenesis and classification of circular RNAs (circRNAs). Pre-mRNA contains a 5′ UTR, exons, introns, and a 3′ UTR. Canonical splicing produces linear mRNA with sequentially joined exons, a 5′ CAP (m⁷G), and a poly(A) tail. In contrast, circRNAs are generated through a non-canonical splicing process termed back-splicing, in which a downstream splice donor is joined to an upstream splice acceptor. circRNA formation can occur via different mechanisms, including lariat-driven circularization, intron-pairing-driven circularization, and RBP-mediated circularization, each of which facilitates the circularization of RNA by bringing distant splice sites into proximity. Based on their composition, circRNAs are classified into ciRNAs, ElcircRNAs, and ecircRNAs, which are formed from introns, both exons and introns, or only exons, respectively

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  Fig. 2. Functional roles and mechanisms of circRNAs in cellular processes: circRNAs, including ecircRNAs and EIcircRNAs, are primarily generated in the nucleus and can either function locally or be transported into the cytoplasm. In the cytoplasm, circRNAs regulate gene expression and cellular functions through various mechanisms: acting as microRNA sponges to prevent miRNA-mediated gene silencing, serving as protein sponges or scaffolds to modulate protein activity or interactions, and functioning as translation templates through internal ribosome entry sites (IRES) to produce peptides. Additionally, circRNAs influence cellular behaviors such as proliferation, migration, and apoptosis, and are secreted via exosomes into the extracellular space, highlighting their potential as diagnostic or prognostic biomarkers

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  Fig. 3. circRNAs associated with CVD and related conditions: Specific circRNAs are implicated in key pathological processes such as atherosclerosis, myocardial infarction, cardiomyopathy, MI, myocardial fibrosis, endothelial cell senescence, CAD, and hypertension. These circRNAs contribute to disease progression by regulating gene expression, cellular stress responses, inflammation, and other molecular mechanisms. Their expression patterns offer insights into disease pathogenesis and also present potential as diagnostic markers or therapeutic targets across a range of cardiovascular conditions