Rapamycin Limits the Growth of Established Experimental Abdominal Aortic Aneurysms
Rapamycin Limits the Growth of Established Experimental Abdominal Aortic Aneurysms
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DOI：
10.1016/j.ejvs.2014.02.006
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发表时间：
2014-05-01
影响因子：
5.7
通讯作者：
Dalman, R. L.
中科院分区：
文献类型：
--
作者：
Rouer, M.;Xu, B. H.;Dalman, R. L.
目的：腹主动脉瘤(AAA)是一种慢性炎症性疾病，约占60岁以上男性的4-8%。没有任何药物策略可以限制疾病进展、动脉瘤破裂或动脉瘤相关死亡。我们检测了雷帕霉素对已建立的实验性AAA的抑制作用。方法：用猪胰腺弹性酶(PPE)输注的方法建立10-12周龄雄性C57BL/6J小鼠AAAs。从注射PPE后4d开始，给予雷帕霉素(5 mg/kg/d)或等体积赋形剂治疗10d。通过系列超声检查监测AAA的进展情况。结果：注射PPE后3天，在赋形剂或雷帕霉素治疗前，两组的动脉瘤均以相同的速度增大。在雷帕霉素组，治疗后第3天和第10天的主动脉扩大分别减少了38%和53%。在组织学分析中，雷帕霉素组的中膜弹性蛋白和平滑肌细胞群相对保留。结论：雷帕霉素抑制实验性动脉瘤的进展，增加了雷帕霉素相关AAA抑制策略的机制靶点的翻译潜能。(C)2014年由爱思唯尔有限公司代表欧洲血管外科学会出版。
Objectives: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease affecting 4-8% of men older than 60 years. No pharmacologic strategies limit disease progression, aneurysm rupture, or aneurysm-related death. We examined the ability of rapamycin to limit the progression of established experimental AAAs.Methods: AAAs were created in 10-12-week-old male C57BL/6J mice via the porcine pancreatic elastase (PPE) infusion method. Beginning 4 days after PPE infusion, mice were treated with rapamycin (5 mg/kg/day) or an equal volume of vehicle for 10 days. AAA progression was monitored by serial ultrasound examination. Aortae were harvested for histological analyses at sacrifice.Results: Three days after PPE infusion, prior to vehicle or rapamycin treatment, aneurysms were enlarging at an equal rate between groups. In the rapamycin group, treatment reduced aortic enlargement by 38%, and 53% at 3 and 10 days, respectively. On histological analysis, medial elastin and smooth muscle cell populations were relatively preserved in the rapamycin group. Rapamycin treatment also reduced mural macrophage density and neoangiogenesis.Conclusion: Rapamycin limits the progression of established experimental aneurysms, increasing the translational potential of mechanistic target of rapamycin-related AAA inhibition strategies. (C) 2014 Published by Elsevier Ltd on behalf of European Society for Vascular Surgery.