Polychlorinated biphenyl 77 augments angiotensin II-induced atherosclerosis and abdominal aortic aneurysms in male apolipoprotein E deficient mice
Polychlorinated biphenyl 77 augments angiotensin II-induced atherosclerosis and abdominal aortic aneurysms in male apolipoprotein E deficient mice
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DOI：
10.1016/j.taap.2011.08.028
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发表时间：
2011-11-15
影响因子：
3.8
通讯作者：
Cassis, Lisa A.
中科院分区：
文献类型：
--
作者：
Arsenescu, Violeta;Arsenescu, Razvan;Cassis, Lisa A.
血管紧张素II（AngII）的高血压小鼠的输液增加动脉粥样硬化，并导致腹主动脉瘤（AAA）的形成。这些AngII诱导的血管病变中的每一种都表现出明显的炎症。以前的研究表明，共面多氯联苯（PCB）促进炎症内皮细胞和脂肪细胞，两种细胞类型的血管紧张素II诱导的血管病变。本研究的目的是测试的假设，即行政PCB 77雄性载脂蛋白E（ApoE）-/-小鼠促进血管紧张素II诱导的动脉粥样硬化和AAA的形成。给雄性ApoE-/-小鼠施用载体或PCB 77（49 mg/kg，i. p.）在第1周和第4周（2次分剂量/周）输注AngII。体重和血清总胆固醇浓度没有受到多氯联苯77的影响。与载体相比，给予PCB 77的AngII输注小鼠的收缩压升高（分别为156 +/- 6 vs 137 +/- 5 mmHg）。与载体相比，给予PCB 77的AngII输注小鼠中动脉粥样硬化病变覆盖的主动脉弓百分比增加（分别为2.0 +/- 0.4 vs 0.9 +/-0.1%）。通过体内超声测定的腹主动脉瘤的管腔直径和切除的肾上动脉瘤的外径在给予PCB 77的AngII输注小鼠中与溶媒相比增加。另外。在给予PCB 77的AngII输注小鼠中，AAA发生率从47%增加到85%。给予多氯联苯77的小鼠的脂肪组织靠近AAAs，表现出促炎细胞因子mRNA丰度增加和肾素-血管紧张素系统组分（血管紧张素原、血管紧张素la型受体（AT 1aR））表达升高。这些结果表明，PCB 77增强AngII诱导的动脉粥样硬化和AAA形成。(C)2011 Elsevier Inc. All rights reserved.
Infusion of angiotensin II (AngII) to hyperlipidemic mice augments atherosclerosis and causes formation of abdominal aortic aneurysms (AAAs). Each of these AngII-induced vascular pathologies exhibit pronounced inflammation. Previous studies demonstrated that coplanar polychlorinated biphenyls (PCBs) promote inflammation in endothelial cells and adipocytes, two cell types implicated in AngII-induced vascular pathologies. The purpose of this study was to test the hypothesis that administration of PCB77 to male apolipoprotein E (ApoE)-/- mice promotes AngII-induced atherosclerosis and AAA formation. Male ApoE-/- mice were administered vehicle or PCB77 (49 mg/kg, i.p.) during week 1 and 4 (2 divided doses/week) of AngII infusion. Body weights and total serum cholesterol concentrations were not influenced by administration of PCB77. Systolic blood pressure was increased in AngII-infused mice administered PCB77 compared to vehicle (156 +/- 6 vs 137 +/- 5 mmHg, respectively). The percentage of aortic arch covered by atherosclerotic lesions was increased in AngII-infused mice administered PCB77 compared to vehicle (2.0 +/- 0.4 vs 0.9 +/- 0.1%, respectively). Lumen diameters of abdominal aortas determined by in vivo ultrasound and external diameters of excised suprarenal aortas were increased in AngII-infused mice administered PCB77 compared to vehicle. In addition. AAA incidence increased from 47 to 85% in AngII-infused mice administered PCB77. Adipose tissue in close proximity to AAAs from mice administered PCB77 exhibited increased mRNA abundance of proinflammatory cytokines and elevated expression of components of the renin-angiotensin system (angiotensinogen, angiotensin type la receptor (AT1aR)). These results demonstrate that PCB77 augments AngII-induced atherosclerosis and AAA formation. (C) 2011 Elsevier Inc. All rights reserved.