腹主动脉瘤(AAA)是一种退行性疾病,其特征是主动脉局部异常扩张,伴有血管平滑肌细胞(VSMC)功能障碍和慢性炎症。VSMC去分化,转分化,基质金属蛋白酶(MMPs)的表达增加是AAA形成的重要原因。我们和其他人以前的研究表明,AnemosideB4(AB4),白头翁皂苷,具有抗炎作用,抗肿瘤,和对VSMC去分化的调节作用。本研究旨在探讨AB4是否抑制AAA的发展及其潜在机制。经由过程运用AngⅡ引诱的体内AAA模子和胆固醇负荷介导的VSMC向巨噬细胞转分化的体外模子,我们的研究表明,AB4可以减轻AAA的发病机制,防止VSMC去分化和转分化为巨噬细胞样细胞,减少血管炎症,并抑制MMP的表达和活性。此外,KLF4过表达减弱了AB4对体外VSMC向巨噬细胞样细胞转化和VSMC炎症的影响。总之,AB4通过抑制KLF4介导的VSMC转分化和炎症来防止小鼠中的AAA形成。我们的研究首次证明了使用AB4进行AAA管理的概念。
Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by local abnormal dilation of the aorta accompanied by vascular smooth muscle cell (VSMC) dysfunction and chronic inflammation. VSMC dedifferentiation,
transdifferentiation, and increased expression of matrix metalloproteinases (MMPs) are essential causes of AAA formation. Previous studies from us and others have shown that Anemoside B4 (AB4), a saponin from Pulsatilla chinensis, has anti-inflammatory, anti-tumor, and regulatory effects on VSMC dedifferentiation. The current study aimed to investigate whether AB4 inhibits AAA development and its underlying mechanisms. By using an Ang II induced AAA model in vivo and cholesterol loading mediated VSMC to macrophage
transdifferentiation model in vitro, our study demonstrated that AB4 could attenuate AAA pathogenesis, prevent VSMC dedifferentiation and
transdifferentiation to macrophage-like cells, decrease vascular inflammation, and suppress MMP expression and activity. Furthermore, KLF4 overexpression attenuated the effects of AB4 on VSMC to macrophage-like cell transition and VSMC inflammation in vitro. In conclusion, AB4 protects against AAA formation in mice by inhibiting KLF4 mediated VSMC
transdifferentiation and inflammation. Our study provides the first proof of concept of using AB4 for AAA management.