Hsa_circ_0001304 promotes vascular neointimal hyperplasia accompanied by autophagy activation

Abstract Aberrant autophagy in vascular smooth muscle cells (VSMCs) is associated with the progression of vascular remodeling diseases caused by neointimal hyperplasia. Platelet-derived growth factor-BB (PDGF-BB)-induced vascular remodeling is accompanied by autophagy activation, however, the involv...

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Main Authors: Shi-Qing Mu, Jia-Jie Lin, Yu Wang, Li-Yun Yang, Sen Wang, Zhao-Yi Wang, An-Qi Zhao, Wen-Jun Luo, Zi-Qi Dong, Yu-Guang Cao, Ze-An Jiang, Si-Fan Wang, Shan-Hu Cao, Li Meng, Yang Li, Shu-Yan Yang, Shao-Guang Sun
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07580-4
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Summary:Abstract Aberrant autophagy in vascular smooth muscle cells (VSMCs) is associated with the progression of vascular remodeling diseases caused by neointimal hyperplasia. Platelet-derived growth factor-BB (PDGF-BB)-induced vascular remodeling is accompanied by autophagy activation, however, the involvement of circular RNAs (circRNAs) remains unclear. Here, we show the role of PDGF-BB-regulated hsa_circ_0001304 (circ-1304) in neointimal hyperplasia and its potential involvement in VSMC autophagy, while also elucidating the potential mechanisms. Functionally, overexpression of circ-1304 promotes VSMC autophagy in vitro and exacerbates neointimal hyperplasia in vivo, and this exacerbation is accompanied by autophagy activation. Mechanistically, circ-1304 acts as a sponge for miR-636, resulting in increased protein levels of YTHDF2. Subsequently, the YTHDF2 protein promotes the degradation of mTOR mRNA by binding to the latter’s m6A modification sites. We demonstrate that PDGF-BB activates VSMC autophagy via circRNA regulation. Therefore, circ-1304 may serve as a potential therapeutic target for vascular remodeling diseases.
ISSN:2399-3642