OBJECTIVE Aortic dissection (AD) is a fatal disease that occurs suddenly without preceding clinical signs or symptoms. Although high salt intake is a proposed risk factor for cardiovascular diseases, the relationship between AD and high salt intake has not been clarified. We examined the effect of high-salt challenge on a mouse AD model. Approach and Results: AD was induced in male mice by continuous infusion of β-aminopropionitrile and Ang II (angiotensin II). High-salt challenge exacerbated aortic wall destruction in AD. Deletion of Il17a (IL-17KO [IL (interleukin)-17A knockout]) did not affect the AD phenotype at baseline, but it abolished the high salt-induced worsening of the aortic destruction. Unexpectedly, aortas of IL-17KO mice exhibited global changes in ECM (extracellular matrix)-related genes without alteration of proinflammatory genes, altered architecture of collagen fibers, and reduced stiffness before AD induction. The aortas of IL-17KO mice were less sensitive to AD-inducing stimuli, as shown by the induction of phenotypic modulation markers SMemb and vimentin, suggesting a reduced stress response. The aortas of IL-17KO mice had a higher population of smooth muscle cells with nuclear-localized phosphorylated Smad2, indicative of TGFβ (transforming growth factor-beta) signal activation. Consistently, pretreatment of smooth muscle cells in culture with IL-17A blunted the activation of Smad2 by TGFβ1. CONCLUSIONS These findings indicate that high salt intake has a worsening effect on AD in the context of high aortic wall stiffness, which is under the control of IL-17A through ECM metabolism. Therefore, salt restriction may represent a low-cost and practical way to reduce AD risk.

中文翻译：

---

高盐摄入会加重小鼠的主动脉夹层：涉及IL（白介素）-17A依赖性ECM（细胞外基质）代谢。

目的主动脉夹层（AD）是一种致命疾病，突然发作而没有任何临床症状或体征。尽管高盐摄入是心血管疾病的危险因素，但AD和高盐摄入之间的关系尚不清楚。我们检查了高盐攻击对小鼠AD模型的影响。方法和结果：雄性小鼠通过连续输注β-氨基丙腈和Ang II（血管紧张素II）来诱导AD。高盐刺激加剧了AD的主动脉壁破坏。Il17a的删除（IL-17KO [IL（interleukin）-17A敲除]）在基线时不影响AD表型，但消除了高盐诱导的主动脉破坏恶化。出乎意料的是，IL-17KO小鼠的主动脉在ECM（细胞外基质）相关基因中表现出整体变化，而促炎基因却没有改变，改变了胶原纤维的结构，并降低了AD诱导前的刚度。IL-17KO小鼠的主动脉对AD诱导的刺激较不敏感，如表型调节标记SMemb和波形蛋白的诱导所示，表明应激反应减少。IL-17KO小鼠的主动脉具有较高数量的平滑肌细胞，其细胞内有核定位的磷酸化Smad2，表明TGFβ（转化生长因子-β）信号激活。一致地，用IL-17A预处理培养的平滑肌细胞会抑制TGFβ1对Smad2的激活。结论这些发现表明，在高主动脉壁僵硬的情况下，高盐摄入量对AD有恶化的作用，这是通过ECM代谢在IL-17A的控制下进行的。所以，