Rouer M, Xu B H, Xuan H J, Tanaka H, Fujimura N, Glover K J, Furusho Y, Gerritsen M, Dalman R L
Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Eur J Vasc Endovasc Surg. 2014 May;47(5):493-500. doi: 10.1016/j.ejvs.2014.02.006. Epub 2014 Mar 12.
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.
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.
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.
Rapamycin limits the progression of established experimental aneurysms, increasing the translational potential of mechanistic target of rapamycin-related AAA inhibition strategies.
腹主动脉瘤（AAA）是一种慢性炎症性疾病，影响4%至8%的60岁以上男性。目前尚无药物策略可限制疾病进展、动脉瘤破裂或与动脉瘤相关的死亡。我们研究了雷帕霉素限制已形成的实验性腹主动脉瘤进展的能力。
通过猪胰弹性蛋白酶（PPE）注射法在10至12周龄雄性C57BL/6J小鼠中制造腹主动脉瘤。在PPE注射后4天开始，小鼠接受雷帕霉素（5毫克/千克/天）或等体积的赋形剂治疗10天。通过系列超声检查监测腹主动脉瘤的进展。在处死时采集主动脉进行组织学分析。
在PPE注射后3天，即在接受赋形剂或雷帕霉素治疗之前，各实验组的动脉瘤以相同速率增大。在雷帕霉素组，治疗在第3天和第10天分别使主动脉扩张减少了38%和53%。组织学分析显示，雷帕霉素组中膜弹性蛋白和平滑肌细胞数量相对得以保留。雷帕霉素治疗还降低了壁层巨噬细胞密度和新生血管形成。
雷帕霉素可限制已形成的实验性动脉瘤的进展，增加雷帕霉素相关的腹主动脉瘤抑制机制靶点策略的转化潜力。
