| Autor: |
Peng Kong, Chang-Lin Li, Yong-Qing Dou, Li Cao, Xiao-Yun Zhang, Wen-Di Zhang, Ze-Qi Bi, Zu-Yi Peng, An-Qi Yan, Mei Han |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cardiovascular Medicine, Vol 8 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2297-055X |
| DOI: |
10.3389/fcvm.2021.724592 |
| Popis: |
Vascular smooth muscle cell (VSMC) senescence is a major driver of neointimal formation. We have demonstrated that circ-Sirt1 derived from the SIRT1 gene suppressed VSMC inflammation and neointimal formation. However, the effect of circ-Sirt1 inhibiting inflammation on VSMC senescence during neointimal hyperplasia remains to be elucidated. Here, we showed that circ-Sirt1 was highly expressed in young and healthy arteries, which was decreased in aged arteries and neointima of humans and mice. Overexpression of circ-Sirt1 delayed Ang II-induced VSMC senescence in vitro and ameliorated neointimal hyperplasia in vivo. Mechanically, circ-Sirt1 inhibited p53 activity at the levels of transcription and post-translation modulation. In detail, circ-Sirt1, on the one hand, interacted with and held p53 to block its nuclear translocation, and on the other hand, promoted SIRT1-mediated p53 deacetylation and inactivation. In conclusion, our data suggest that circ-Sirt1 is a novel p53 repressor in response senescence-inducing stimuli, and targeting circ-Sirt1 may be a promising approach to ameliorating aging-related vascular disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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