Zhou Yating, Chen Yanyu, Cui Yuting, Gan Ni, Xiang Qiong, Li Man, Zeng Wen, Zheng Xi-Long, Dai Xiaoyan, Peng Juan, Tang Zhihan
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Shaoyang Branch of Key Laboratory for Arteriosclerology of Hunan Province, The Central Hospital of Shaoyang, Shaoyang, 421001, China.
J Cardiovasc Transl Res. 2025 Apr 21. doi: 10.1007/s12265-025-10621-2.
Ferroptosis plays a key role in abdominal aortic aneurysm (AAA) development. This study explores whether and how ferroptosis regulates AAA progression. Ferroptosis was confirmed in human AAA tissue. In vitro experiments with primary mouse vascular smooth muscle cells (VSMCs) and abdominal aortic rings revealed that angiotensin II (Ang II) triggered ferroptosis in VSMCs. Ferrostatin-1 (Fer-1), a potent ferroptosis inhibitor, effectively suppressed this effect. Additionally, the ferroptosis inducer erastin and Ang II can both promoted pathological remodeling of abdominal aortic rings, but Fer-1 significantly suppressed these effects. In AAA mouse model, Fer-1 treatment reduced AAA formation. Mechanistically, RNA-sequencing analysis revealed that Fer-1 regulates VSMC contractile function, suppresses inflammation, and mitigates extracellular matrix remodeling. These findings highlight the critical role of VSMC ferroptosis in AAA pathogenesis and demonstrate that ferroptosis inhibition effectively reduces pathological vascular remodeling, making it a promising therapeutic strategy for preventing AAA.
铁死亡在腹主动脉瘤（AAA）的发展中起关键作用。本研究探讨铁死亡是否以及如何调节AAA的进展。在人类AAA组织中证实了铁死亡。对原代小鼠血管平滑肌细胞（VSMC）和腹主动脉环进行的体外实验表明，血管紧张素II（Ang II）可引发VSMC中的铁死亡。铁死亡抑制剂Ferrostatin-1（Fer-1）有效抑制了这种作用。此外，铁死亡诱导剂erastin和Ang II均可促进腹主动脉环的病理重塑，但Fer-1可显著抑制这些作用。在AAA小鼠模型中，Fer-1治疗可减少AAA的形成。从机制上讲，RNA测序分析表明，Fer-1可调节VSMC的收缩功能，抑制炎症，并减轻细胞外基质重塑。这些发现突出了VSMC铁死亡在AAA发病机制中的关键作用，并表明抑制铁死亡可有效减少病理性血管重塑，使其成为预防AAA的一种有前景的治疗策略。
