主动脉瘤带走爱因斯坦？

研究发现补充亚精胺或可抑制腹主动脉瘤的发展

【文献解读】

美国心脏协会杂志（Journal of the American Heart Association）于2020年4月发布一篇文章，指出实验性腹主动脉瘤模型小鼠补充亚精胺可以维持其主动脉结构完整性，减弱主动脉炎性浸润，增加自噬相关蛋白的表达，抑制实验性腹主动脉瘤的发展。

研究选择C57BL/6J雄性小鼠，通过向主动脉内输注猪胰弹性蛋白酶诱发了实验性腹主动脉瘤，随后在饮用水中添加亚精胺进行治疗。结果发现，小鼠在接受亚精胺治疗后血浆中亚精胺水平显著提高，由对照组的4μM/mL增加至6μM/mL。并且，亚精胺的摄入不影响小鼠的摄食量和体重。在腹主动脉瘤发展方面，对照组腹主动脉瘤发病率为100%，亚精胺治疗后发病率降至72.22%，最大主动脉直径由对照组的1.67mm降至1.26mm。进一步组织观察发现，用亚精胺治疗的小鼠动脉弹性蛋白破坏和平滑肌细胞耗竭均显著减弱。这些结果表明了亚精胺对腹主动脉瘤的发展有抑制作用。

此外，亚精胺治疗可减少主动脉炎症反应，表现在巨噬细胞浸润程度减小和实验性腹主动脉瘤中的循环炎症细胞降低。研究者在收集的临床腹主动脉瘤患者样品中检测到自噬功能失调，而在小鼠中，亚精胺治疗增加了自噬相关蛋白的表达，这可能是亚精胺治疗腹主动脉瘤的潜在靶标。

作者指出，亚精胺是日常饮食中存在的天然化合物，外源补充后不太可能发生不良反应，因此在临床中作为腹主动脉瘤的治疗药物可能非常有前途。

【文献节选】

Background

The protective effects of polyamines on cardiovascular disease have been demonstrated in many studies. However, the roles of spermidine, a natural polyamine, in abdominal aortic aneurysm (AAA) disease have not been studied. In this study, we investigated the influence and potential mechanisms of spermidine treatment on experimental AAA disease.

Methods and Results

Experimental AAAs were induced in 8- to 10-week-old male C57BL/6J mice by transient intra-aortic infusion of porcine pancreatic elastase. Spermidine was administered via drinking water at a concentration of 3 mmol/L. Spermidine treatment prevented experimental AAA formation with preservation of medial elastin and smooth muscle cells. In immunostaining, macrophages, T cells, neutrophils, and neovessels were significantly reduced in aorta of spermidine-treated, as compared with vehicle‐treated elastase‐infused mice. Additionally, flow cytometric analysis showed that spermidine treatment reduced aortic leukocyte infiltration and circulating inflammatory cells. Furthermore, we demonstrated that spermidine treatment promoted autophagy‐related proteins in experimental AAAs using Western blot analysis, immunostaining, and transmission electron microscopic examination. Autophagic function was evaluated for human abdominal aneurysmal and nonaneurysmal adjacent aortae from AAA patients using Western blot analysis and immunohistochemistry. Dysregulated autophagic function, as evidenced by increased SQSTM1/p62 protein and phosphorylated mTOR, was found in aneurysmal, as compared with nonaneurysmal, aortic segments.

Conclusions

Our results suggest that spermidine supplementation limits experimental AAA formation associated with preserved aortic structural integrity, attenuated aortic inflammatory infiltration, reduced circulating inflammatory monocytes, and increased autophagy-related proteins. These findings suggest that spermidine may be a promising treatment for AAA disease.

【原文标题】Spermidine Suppresses Development of Experimental Abdominal Aortic Aneurysms

【标题翻译】亚精胺抑制实验性腹主动脉瘤的发展

【发布杂志】Journal of the American Heart Association

【发布时间】2020.04

【影响因子】4.605

【原文链接】

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428527/