BACKGROUND Dietary high salt (HS) intake has a strong impact on cardiovascular diseases. Here, we investigated the link between HS-aggravated immune responses and the development of hypertensive vascular disease. METHODS ApolipoproteinE-deficient mice were transiently treated with HS (1% NaCl) via drinking water for 2 weeks, followed by a washout period, and subsequent Ang II (angiotensin II) infusion (1000 ng/kg per min for 10 days) to induce abdominal aortic aneurysms/dissections and inflammation. RESULTS While transient HS intake alone triggered nonpathologic infiltration of activated T cells into the aorta, subsequent Ang II infusion increased mortality and the incidence of abdominal aortic aneurysms/dissections and atherosclerosis compared with hypertensive control mice. There were no differences in blood pressure between both groups. In transient HS-treated hypertensive mice, the aortic injury was associated with increased inflammation, accumulation of neutrophils, monocytes, CD69+CD4+ T cells, as well as CD4+ and CD8+ memory T cells. Mechanistically, transient HS intake increased expression levels of aortic RORγt as well as splenic CD4+TH17 and CD8+TC1 T cells in Ang II-treated mice. Isolated aortas of untreated mice were incubated with supernatants of TH17, TH1, or TC1 cells polarized in vitro under HS or normal conditions which revealed that secreted factors of HS-differentiated TH17 and TC1 cells, but not TH1 cells accelerated endothelial dysfunction. CONCLUSIONS Our data suggest that transient HS intake induces a subclinical T-cell-mediated aortic immune response, which is enhanced by Ang II. We propose a 2-hit model, in which HS acts as a predisposing factor to enhance hypertension-induced TH17 and TC1 polarization and aortic disease.

中文翻译：

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短暂的高盐摄入量会促进 T 细胞介导的高血压血管损伤。


背景 膳食高盐 （HS） 摄入量对心血管疾病有很大影响。在这里，我们研究了 HS 加重的免疫反应与高血压血管疾病发展之间的联系。方法 载脂蛋白 E 缺陷小鼠通过饮水用 HS （1% NaCl） 瞬时处理 2 周，然后是清除期，随后输注 Ang II（血管紧张素 II.）[每分钟 1000 ng/kg，持续 10 天]以诱导腹主动脉瘤/夹层和炎症。结果虽然单独的短暂 HS 摄入会触发活化的 T 细胞非病理性浸润到主动脉中，但与高血压对照小鼠相比，随后的 Ang II 输注增加了死亡率和腹主动脉瘤/夹层和动脉粥样硬化的发生率。两组之间的血压没有差异。在短暂性 HS 治疗的高血压小鼠中，主动脉损伤与炎症增加、中性粒细胞、单核细胞、CD69+CD4+ T 细胞以及 CD4+ 和 CD8+ 记忆 T 细胞的积累有关。从机制上讲，短暂的 HS 摄入增加了 Ang II 处理小鼠主动脉 RORγt 以及脾 CD4+TH17 和 CD8+TC1 T 细胞的表达水平。将未处理小鼠的分离主动脉与在 HS 或正常条件下体外极化的 TH17、TH1 或 TC1 细胞的上清液一起孵育，结果显示 HS 分化的 TH17 和 TC1 细胞的分泌因子，而不是 TH1 细胞的分泌因子加速了内皮功能障碍。结论 我们的数据表明，短暂的 HS 摄入会诱导亚临床 T 细胞介导的主动脉免疫反应，这种反应会因 Ang II 而增强。我们提出了一个 2-hit 模型，其中 HS 作为增强高血压诱导的 TH17 和 TC1 极化和主动脉疾病的诱发因素。