Efficacy of Simvastatin in Reducing Aortic Dilatation in Mouse Models of Abdominal Aortic Aneurysm
Efficacy of Simvastatin in Reducing Aortic Dilatation in Mouse Models of Abdominal Aortic Aneurysm
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DOI：
10.1007/s10557-010-6262-8
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发表时间：
2010-12-01
影响因子：
3.4
通讯作者：
Rush, Catherine
中科院分区：
文献类型：
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作者：
Golledge, Jonathan;Cullen, Bradford;Rush, Catherine
目前尚无治疗腹主动脉瘤（AAA）的有效药物。本研究的目的是评估辛伐他汀在两种小鼠模型中抑制主动脉扩张的能力。在两种易患动脉粥样硬化的小鼠品系中诱导 AAA。首先，给 11 周龄雄性载脂蛋白 E 缺陷型 (ApoE(-/-)) 小鼠注射载体对照 (n = 27) 或辛伐他汀 (50 mg/kg/d，n = 27)，然后皮下注射血管紧张素 II (1 μg/kg/min)，持续 4 周。其次，对 9 周龄雄性低密度脂蛋白受体缺陷 (LDLR(-/-)) 小鼠进行高脂肪饮食喂养，然后给予载体对照 (n = 17) 或辛伐他汀 (50 mg/kg/d，n = 18)，并在 14 至 18 周龄期间注射血管紧张素 II。随后收获主动脉，测量最大肾上主动脉直径，通过苏丹IV染色评估主动脉弓动脉粥样硬化，并提取血液以测量血清脂质。在LDLR(-/-)小鼠中，在收获主动脉之前还通过超声测量了肾上主动脉直径。在ApoE(-/-)小鼠中，接受辛伐他汀的动物的肾上主动脉直径稍小，尽管巨噬细胞浸润减少，但没有显着变化。接受辛伐他汀治疗的 LDLR(-/-) 小鼠的主动脉弓粥样硬化明显减少，肾上主动脉直径显着减小。辛伐他汀对两种小鼠模型的血脂均没有有利的改变。在这项涉及两种 AAA 小鼠模型的研究中，辛伐他汀在限制主动脉扩张方面的功效有限，但在减少动脉粥样硬化进展方面具有显着的能力。
Currently there is no effective drug therapy for abdominal aortic aneurysm (AAA). The aim of this study was to assess the ability of simvastatin to inhibit aortic dilatation in two mouse models.AAAs were induced in two mice strains predisposed to atherosclerosis. Firstly, 11 weeks old male apolipoprotein E deficient (ApoE(-/-)) mice were given vehicle control (n = 27) or simvastatin (50 mg/kg/d, n = 27) prior to being infused with angiotensin II (1 mu g/kg/min) subcutaneously for 4 weeks. Secondly, 9 weeks old male low-density lipoprotein receptor deficient (LDLR(-/-)) mice were fed a high fat diet, then given vehicle control (n = 17) or simvastatin (50 mg/kg/d, n = 18) and from 14 to 18 weeks of age infused with angiotensin II. Subsequently aortas were harvested, maximum suprarenal aortic diameter measured, aortic arch atheroma assessed by sudan IV staining and blood extracted to measure serum lipids. In the LDLR(-/-) mice the suprarenal aortic diameter was also measured by ultrasound prior to aortic harvesting.In ApoE(-/-) mice suprarenal aortic diameters were modestly smaller in animals receiving simvastatin without significant change despite reduction in macrophage infiltration. Aortic arch atheroma was substantially reduced in LDLR(-/-) mice receiving simvastatin with borderline significant reduction in suprarenal aortic diameters. Simvastatin did not favourably modify serum lipids in either mouse model.In this study involving two mouse models of AAA, simvastatin had limited efficacy in restricting aortic dilatation but substantial ability to reduce atheroma progression.