Key result
circSOD2 knockdown attenuates injury-induced neointima formation and SMC proliferation in a rat model.
Why the study?
Vascular smooth muscle cell proliferation contributes to neointima formation following vascular injury, but the role of circular RNA in these processes is largely unknown.
CircSOD2 acts as a sponge for miR-206 to upregulate NOTCH3 signaling, promoting SMC proliferation and neointima formation, making it a potential therapeutic target for proliferative vascular diseases.
Suggests circSOD2 as a therapeutic target in restenosis; hypothesis-generating in rodents and requires human validation.
OBJECTIVE: Vascular smooth muscle cell (SMC) proliferation contributes to neointima formation following vascular injury. Circular RNA-a novel type of noncoding RNA with closed-loop structure-exhibits cell- and tissue-specific expression patterns. However, the role of circular RNA in SMC proliferation and neointima formation is largely unknown. The objective of this study is to investigate the role and mechanism of circSOD2 in SMC proliferation and neointima formation. Approach and Results: Circular RNA profiling of human aortic SMCs revealed that PDGF (platelet-derived growth factor)-BB up- and downregulated numerous circular RNAs. Among them, circSOD2, derived from back-splicing event of SOD2 (superoxide dismutase 2), was significantly enriched. Knockdown of circSOD2 by short hairpin RNA blocked PDGF-BB-induced SMC proliferation. Inversely, circSOD2 ectopic expression promoted SMC proliferation. Mechanistically, circSOD2 acted as a sponge for miR-206, leading to upregulation of NOTCH3 (notch receptor 3) and NOTCH3 signaling, which regulates cyclin D1 and CDK (cyclin-dependent kinase) 4/6. In vivo studies showed that circSOD2 was induced in neointima SMCs in balloon-injured rat carotid arteries. Importantly, knockdown of circSOD2 attenuated injury-induced neointima formation along with decreased neointimal SMC proliferation. CONCLUSIONS: CircSOD2 is a novel regulator mediating SMC proliferation and neointima formation following vascular injury. Therefore, circSOD2 could be a potential therapeutic target for inhibiting the development of proliferative vascular diseases.
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A 2021 study studied Vascular smooth muscle cell proliferation and neointima formation. circSOD2 knockdown vs. Control was evaluated on SMC proliferation and neointima formation. Knockdown of circSOD2 attenuated injury-induced neointima formation and decreased neointimal smooth muscle cell proliferation in a rat carotid artery model.
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