CircRNA-TMEM71 Inhibits Human Aortic Smooth Muscle Cell Ferroptosis and Prevents Aortic Dissection Formation Through IGF2BP3-Mediated Stability of FSP1.

Abstract

BACKGROUND: Aortic dissection (AD) is a severe cardiovascular disease with high mortality and limited treatment options. Previous studies have shown that circular RNA and ferroptosis play significant roles in various cardiovascular diseases, regulating disease progression. However, there is little research on how circular RNA regulates ferroptosis in vascular smooth muscle cells during AD progression, and the specific molecular mechanisms remain a mystery. METHODS AND RESULTS: In this study, we found that circTMEM71 is downregulated in AD and angiotensin II-induced human aortic smooth muscle cells and inhibits ferroptosis. Mechanistically, circTMEM71 can bind to IGF2BP3 (insulin-like growth factor II mRNA-binding protein 3) and inhibit its degradation via the ubiquitin-mediated proteasome pathway. Additionally, IGF2BP3 can bind to FSP1 (ferroptosis suppressor protein 1) mRNA, enhancing its stability and thus suppressing cellular ferroptosis. Finally, we also confirmed that circTMEM71 can alleviate symptoms of AD in Sprague-Dawley rats through in vivo experiments, including histopathologic changes and ferroptosis. CONCLUSIONS: In summary, our study suggested that circTMEM71 is a potential therapeutic target for AD and highlights its role in inhibiting ferroptosis in vascular smooth muscle cells.