Simvastatin suppresses experimental aortic aneurysm expansion
Simvastatin suppresses experimental aortic aneurysm expansion
复制标题
DOI：
10.1016/j.jvs.2005.08.007
复制
发表时间：
2006-01-01
影响因子：
4.3
通讯作者：
Carey, DJ
中科院分区：
文献类型：
--
作者：
Kalyanasundaram, A;Elmore, JR;Carey, DJ
目的：腹主动脉瘤(AAA)的形成是由基质金属蛋白酶(MMPs)介导的炎症和细胞外基质(ECM)重塑的结果。羟甲基戊二酰辅酶A抑制剂(他汀类)虽然在临床上被用作降脂药物，但也被证明具有抗炎作用。本研究旨在探讨羟甲基戊二酰辅酶A抑制剂辛伐他汀是否能抑制弹性酶诱导的大鼠AAA模型的动脉瘤形成。方法：在成年雄性Wistar大鼠肾下动脉段注入弹性酶建立动脉瘤模型。这些大鼠被随机分为辛伐他汀(n=17)和安慰剂(n=17)，从手术前一天开始每天洗胃。术后第7天处死大鼠，取肾下主动脉，分别于输液前、输液后即刻和切取时测量主动脉内径。免疫印迹法检测蛋白表达。用Affymetrix U34A大鼠基因组芯片进行基因表达谱分析，以确定辛伐他汀治疗后基因表达的变化。结果：辛伐他汀治疗组的平均动脉瘤直径显著小于对照组(3.4+/-0.08 mm比4.3+/-0.19 mm；P=0.0001)。用辛伐他汀治疗的动物，主动脉中的基质金属蛋白酶-9和核因子-kappaB的蛋白水平降低。基因芯片分析发现315个基因的表达发生了显著的变化(P
Objective: Abdominal aortic aneurysm (AAA) formation is a result of inflammation and extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases (MMPs). Hydroxymethylglutaryl-coenzyme A inhibitors (statins), although clinically used as lipid-lowering agents, have also been demonstrated to have anti-inflammatory effects. This study was designed to determine whether the hydroxymethylglutaryl-coenzyme A inhibitor simvastatin suppresses aneurysm formation in an elastase-induced rat AAA model.Methods: Aneurysms were created in adult male Wistar rats by infusion of elastase into isolated infrarenal aortic segments. The rats were randomized to receive either simvastatin (n = 17) or placebo (n = 17) by gastric lavage daily starting the day before surgery. The rats were euthanized and the infrarenal aortas harvested on postoperative day 7. Aortic diameters were measured before infusion, immediately after infusion, and at the time of harvesting. Protein expression was measured by immunoblot analysis. Gene expression profiling using Affymetrix U34A rat genome chips was performed to identify changes in gene expression caused by simvastatin treatment.Results: Mean aneurysm diameter was significantly less in the simvastatin treatment group compared with controls (3.4 +/- 0.08 mm vs 4.3 +/- 0.19 mm; P =.0001). MMP-9 and nuclear factor-kappa B protein levels were decreased in the aortas of simvastatin-treated animals. Gene microarray analysis revealed 315 genes with statistically significant changes in expression (P