Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong, P.R. China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Shandong, P.R. China.
Hum Gene Ther. 2018 Dec;29(12):1387-1395. doi: 10.1089/hum.2016.144. Epub 2018 Nov 13.
Recent studies have demonstrated that angiotensin-converting enzyme 2 (ACE2) plays an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, few studies have reported the direct effect of ACE2 overexpression on the aneurysm. This study hypothesized that the overexpression of ACE2 may prevent the pathogenesis of aneurysms by decreasing RAS activation. Thirty-nine mice were randomly assigned to three groups ( = 13 in each group): the Ad.ACE2 group, the group, and a control group. After 8 weeks of treatment, abdominal aortas with AAAs were obtained for hematoxylin and eosin staining, Verhoeff Van Gieson staining, immunohistochemistry, and Western blotting. The incidence and severity of AAAs, macrophage infiltration, and MMP protein expression were all recorded. The results showed that ACE2 gene transfer significantly decreased the occurrence of AAAs and inhibited AAA formation in mice by inhibiting the inflammatory response and MMP activation, and the mechanisms may involve decreased ERK and Ang II-nuclear factor kappa B signaling pathways.
最近的研究表明,血管紧张素转换酶 2(ACE2)在腹主动脉瘤(AAA)的发病机制中起着重要作用。然而,很少有研究报道 ACE2 的过表达对动脉瘤的直接影响。本研究假设 ACE2 的过表达可能通过减少 RAS 激活来预防动脉瘤的发病机制。39 只小鼠被随机分为三组(每组 13 只):Ad.ACE2 组、 组和对照组。治疗 8 周后,取AAA 腹主动脉进行苏木精和伊红染色、Verhoeff Van Gieson 染色、免疫组织化学和 Western blot 分析。记录 AAA 的发生率和严重程度、巨噬细胞浸润和 MMP 蛋白表达。结果表明,ACE2 基因转移通过抑制炎症反应和 MMP 激活,显著降低了 小鼠 AAA 的发生和形成,其机制可能涉及减少 ERK 和 Ang II-核因子 kappa B 信号通路。