Pharmacotherapy for abdominal aortic aneurysm by the inhibition of c=jun N-terminal kinase

腹主动脉瘤是老年人中的常见疾病，当外科治疗不适用时，会导致主动脉进行性扩张和破裂，死亡率高。虽然非手术治疗的主动脉瘤是期待已久，但很少有选择，因为它的分子发病机制仍然是难以捉摸的。我们确定JNK作为近端信号分子在主动脉瘤的发病机制。人腹主动脉瘤组织中磷酸化JNK水平高。我们表明，JNK程序的基因表达模式在不同的细胞类型，这合作增强细胞外基质的降解，同时抑制细胞外基质的生物合成酶。选择性JNK抑制在体内不仅防止了主动脉瘤的发展，但也造成了两个小鼠模型中建立的主动脉瘤消退。因此，JNK促进了主动脉瘤组织中细胞外基质的异常代谢，可能是一个新的治疗靶点。

Abdominal aortic aneurysm is a common disease among elderly people that, when surgical treatment is inapplicable, results in progressive expansion and rupture of the aorta with high mortality. Although non-surgical treatment for aortic aneurysm is much awaited, few opt ions are available because its molecular pathogenesis remains elusive. We identified JNK as a proximal signaling molecule in the pathogenesis of aortic aneurysm. Human abdominal aortic aneurysm tissue showed high level of phospho-JNK. We show that JNK programs a gene expression pattern in different cell types, which cooperatively enhances the degradation of the extracellular matrix, while suppressing biosynthetic enzymes of the extracellular matrix. Selective JNK inhibition in vivo not only prevented the development of aortic aneurysm but also caused regression of established aortic aneurysm in two mouse models. Therefore, JNK promotes abnormal extracellular matrix metabolism in the tissue of aortic aneurysm and may represent a novel therapeutic target.