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ADAM10 attenuates the development of abdominal aortic aneurysms in a mouse model.
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2021-09-07 , DOI: 10.3892/mmr.2021.12414
Qiu Renfeng 1 , Chen Shuxiao 1 , Gao Peixian 1 , Luo Kun 1 , Feng Xuedong 2 , Yuan Hai 1 , Wu Xuejun 1 , Li Gang 1
Affiliation  

An abdominal aortic aneurysm (AAA) is a life‑threatening disease associated with a high mortality rate. At present, surgery or minimally invasive interventions are used in clinical treatment, especially for small aneurysms. However, the benefits of surgical repair are not obvious, and AAA ruptures can be prevented by aneurysm therapy to inhibit the growth of small aneurysms. Therefore, evaluating effective drugs to treat small AAAs is urgently required. Chronic inflammation is the main pathological feature of aneurysmal tissues. The aim of the present study was to investigate the protective role and underlying mechanism of ADAM metallopeptidase domain 10 (ADAM10). In the present study, a mouse model of AAA was established via porcine pancreatic elastase perfusion for 5 min per day for 14 days. ADAM10 (6 mg/kg) was injected intraperitoneally following 3 days of porcine pancreatic elastase perfusion in the ADAM10 group and the treatment continued for 10 days. The maximum inner luminal diameters of the infrarenal abdominal aortas were measured using an animal ultrasound system. The levels of high mobility group box 1 (HMGB1) and soluble receptor for advanced glycosylation end products in serum samples were measured by ELISA. Hematoxylin and eosin and elastin van Gieson staining were performed to observe morphology, integrity of the elastin layers and elastin degradation. CD68 expression was detected by immunohistochemical staining. Reverse transcription‑quantitative PCR and western blotting were used for detection of mRNA and protein levels. The gelatinolytic activities of MMP‑2 and MMP‑9 were quantified via gelatin zymography analysis. These results showed that ADAM10 inhibited HMGB1/RAGE/NF‑κB signaling and MMP activity in the pathogenesis of pancreatic elastase‑induced AAA, which provide insight into the molecular mechanism of AAA and suggested that ADAM10 may be a potential therapeutic target for AAA.

中文翻译:

ADAM10 可减轻小鼠模型中腹主动脉瘤的发展。

腹主动脉瘤 (AAA) 是一种与高死亡率相关的危及生命的疾病。目前临床治疗多采用手术或微创介入治疗,尤其是对小动脉瘤的治疗。但手术修复的好处并不明显,可以通过动脉瘤治疗抑制小动脉瘤的生长来预防AAA破裂。因此,迫切需要评估治疗小 AAA 的有效药物。慢性炎症是动脉瘤组织的主要病理特征。本研究的目的是研究 ADAM 金属肽酶结构域 10 (ADAM10) 的保护作用和潜在机制。在本研究中,通过每天灌注猪胰弹性蛋白酶 5 分钟,连续 14 天建立了 AAA 小鼠模型。ADAM10组在猪胰弹性蛋白酶灌注3天后腹腔注射ADAM10(6 mg/kg),持续治疗10天。使用动物超声系统测量肾下腹主动脉的最大内腔直径。ELISA法测定血清样品中高迁移率族框1(HMGB1)和晚期糖基化终产物可溶性受体的水平。进行苏木精和伊红以及弹性蛋白van Gieson染色以观察弹性蛋白层的形态、完整性和弹性蛋白降解。通过免疫组织化学染色检测CD68表达。逆转录定量 PCR 和蛋白质印迹用于检测 mRNA 和蛋白质水平。通过明胶酶谱分析定量 MMP-2 和 MMP-9 的明胶分解活性。
更新日期:2021-09-07
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