Key result
Circ-Sirt1 inhibits VSMC proliferation and neointimal formation by directly binding c-Myc.
Why the study?
Restenosis is driven by excessive vascular smooth muscle cell proliferation, but little is known about the role of circRNAs in VSMC proliferation and phenotypic switching.
circ-Sirt1 inhibits VSMC proliferation and neointimal formation via the c-Myc/cyclin B1 axis, suggesting a potential therapeutic target for restenosis.
May support circ-Sirt1 as restenosis target in models; leaves open human validation before any clinical consideration.
Vascular smooth muscle cells (VSMCs) are an important cellular component of the vascular wall. Restenosis is mainly due to VSMC excessive proliferation. However, little is known about the role of circRNAs in VSMC proliferation and phenotypic switching. Herein, using fluorescence in situ hybridization assay and quantitative real-time polymerase chain reaction, we found that circ-Sirt1 was markedly downregulated in neointimal formation after injury and in VSMCs treated with platelet-derived growth factor BB (PDGF-BB). Bromodeoxyuridine and MTT assays confirmed the inhibitory role of circ-Sirt1 on cell proliferation. Mechanistically, circ-Sirt1 was mainly expressed in the cytoplasm of VSMCs. Through RNA immunoprecipitation and RNA pull-down assays, we found that circ-Sirt1 bound with c-Myc, which protein associated with proliferation of VSMCs. Chromatin immunoprecipitation assay also provided evidence that the overexpression of circ-Sirt1 almost ceased PDGF-BB-induced binding of c-Myc to the promoter of cyclin B1 in VSMCs. These results indicated that circ-Sirt1 had an inhibitory effect on c-Myc activity, providing a mechanism for suppressing PDGF-BB-induced VSMC proliferation by direct interactions with c-Myc and its sequestration in the cytoplasm. Overall, our study demonstrated that a previously unrecognized circ-Sirt1/c-Myc/cyclin B1 axis in VSMCs mediates neointimal formation following injury.
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Huang et al. (2022) studied Restenosis and neointimal formation. circ-Sirt1 was evaluated on Vascular smooth muscle cell proliferation and neointimal formation. Circ-Sirt1 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and neointimal formation by directly binding to c-Myc and preventing its binding to the cyclin B1 promoter.
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