Excessive Methionine Supplementation Exacerbates the Development of Abdominal Aortic Aneurysm in Rats
Excessive Methionine Supplementation Exacerbates the Development of Abdominal Aortic Aneurysm in Rats
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DOI：
10.1159/000501313
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发表时间：
2019-10-01
影响因子：
1.7
通讯作者：
Hu, Xinhua
中科院分区：
文献类型：
--
作者：
Fan, Yichuan;Li, Nan;Hu, Xinhua
目的：甲硫氨酸（Met）和腹主动脉瘤（AAA）之间的关系已被证实，但控制这种关联的机制仍不清楚。本研究探讨了高甲硫氨酸血症（HMet）对AAA发生的潜在作用。研究方法：将60只雄性Sprague-Dawley大鼠分为4组（每组n = 15），通过腔内猪胰弹性蛋白酶（PPE）输注诱导AAA模型。从术前1周至术后4周，通过胃内给药（1 g/kg体重/天）提供Met。超声测量主动脉直径。手术后4周收集主动脉，并进行生化分析，组织学测定和透射电子显微镜检查。结果如下：补充Met 5周后，HMet增加了HMet + PPE组的扩张率，并在HMet和HMet + PPE大鼠中诱导了高同型半胱氨酸血症。在HMet + PPE大鼠中检测到基质金属蛋白酶-2（MMP-2）、骨桥蛋白和白细胞介素-6表达增加。此外，在HMet + PPE组中检测到增加的自噬。结论：这项研究表明，HMet可能会加剧AAA的形成，这是由于部分通过增强MMP-2和炎症反应增加了扩张率。
Objective: The relationship between methionine (Met) and abdominal aortic aneurysm (AAA) has been previously demonstrated, but the mechanisms controlling this association remain unclear. This study investigated the potential contribution of hypermethioninemia (HMet) to the development of AAA. Methods: A model of AAA was induced by intraluminal porcine pancreatic elastase (PPE) infusion in 60 male Sprague-Dawley rats divided into 4 groups (n = 15 per group). Met was supplied by intragastric administration (1 g/kg body weight/day) from 1 week before surgery until 4 weeks after surgery. The aortic diameter was measured by ultrasound. Aortas were collected 4 weeks after surgery and subjected to biochemical analysis, histological assays, and transmission electron microscopy. Results: After 5 weeks of Met supplementation, HMet increased the dilation ratio of the HMet + PPE group, and hyperhomocysteinemia was also induced in HMet and HMet + PPE rats. Increased matrix metalloproteinase-2 (MMP-2), osteopontin, and interleukin-6 expression was detected in HMet + PPE rats. Furthermore, increased autophagy was detected in the HMet + PPE group. Conclusion: This study demonstrates that HMet may exacerbate the formation of AAA due to the increased dilation ratio partially via enhancing MMP-2 and inflammatory responses.