成纤维细胞生长因子 21 通过 PI3K/AKT/mTOR 通路促进血管紧张素 II 诱导的腹主动脉瘤。
FGF21 promotes angiotensin II-induced abdominal aortic aneurysm via PI3K/AKT/mTOR pathway.
机构信息
Department of General Surgery, Changshu Hospital Affiliated to Soochow University, Changshu, China.
出版信息
Vascular. 2024 Dec;32(6):1369-1377. doi: 10.1177/17085381231192688. Epub 2023 Jul 31.
BACKGROUND
Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disorder with a high mortality rate. It was previously reported that fibroblast growth factor 21 (FGF21) was highly expressed in AAA patients. Nonetheless, its underlying mechanism in AAA progression is unclarified.
METHODS
Angiotensin II (Ang-II) was used to induce AAA in human aortic vascular smooth muscle cells (HASMCs) and mouse models. Western blotting and RT-qPCR were utilized for measuring protein and RNA levels. Immunofluorescence staining was utilized for detecting LC3B expression in HASMCs. Elastica van Gieson staining was conducted for histological analysis of the abdominal aortas of mice.
RESULTS
FGF21 displayed a high level in Ang-II-stimulated HASMCs and AAA mice. FGF21 depletion ameliorated abdominal aorta dilation and Ang-II-triggered pathological changes in mice. FGF21 silencing hindered autophagy and PI3K/AKT/mTOR pathway.
CONCLUSIONS
FGF21 contributes to AAA progression by enhancing autophagy and activating PI3K/AKT/mTOR pathway.
背景
腹主动脉瘤（AAA）是一种具有高死亡率的潜在致命血管疾病。此前有报道称，成纤维细胞生长因子 21（FGF21）在 AAA 患者中高表达。然而，其在 AAA 进展中的潜在机制尚不清楚。
方法
血管紧张素 II（Ang-II）被用于诱导人主动脉血管平滑肌细胞（HASMCs）和小鼠模型发生 AAA。Western blot 和 RT-qPCR 用于测量蛋白和 RNA 水平。免疫荧光染色用于检测 HASMCs 中 LC3B 的表达。弹性纤维 Van Gieson 染色用于分析小鼠腹主动脉的组织学变化。
结果
FGF21 在 Ang-II 刺激的 HASMCs 和 AAA 小鼠中呈现高表达。FGF21 耗竭改善了小鼠的腹主动脉扩张和 Ang-II 引发的病理变化。FGF21 沉默抑制了自噬并激活了 PI3K/AKT/mTOR 通路。
结论
FGF21 通过增强自噬并激活 PI3K/AKT/mTOR 通路促进 AAA 的进展。
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