Inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation
Inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation
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DOI：
10.1016/j.biopha.2009.02.006
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发表时间：
2009-12-01
影响因子：
7.5
通讯作者：
Sata, Masataka
中科院分区：
文献类型：
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作者：
Fukuda, Daiju;Enomoto, Soichiro;Sata, Masataka
近年来研究表明，肾素-血管紧张素系统（RAS）在动脉粥样硬化的发病过程中起重要作用。据报道，用血管紧张素II型受体阻滞剂（ARBs）或血管紧张素转换酶抑制剂（ACEIs）抑制RAS可有效预防动脉粥样硬化。在这里，我们研究了ARB或/和ACEI对载脂蛋白E （ApoE）缺陷小鼠动脉粥样硬化发展和表皮周围炎症的影响。RT-PCR显示主要RAS成分在主动脉周围组织中表达。灌注Angⅱ显著增加了骨髓源性细胞在新生内膜（p < 0.05）和主动脉周围组织的聚集（p < 0.01）。从12周龄开始，用TA606A （10 mg/kg/天，ARB）、咪唑四月Q mg/kg/天，ACEI)或TA606A加咪唑四月（TA606A 10 mg/kg/天+咪唑四月3 mg/kg/天，ARB + ACEI）治疗雄性ApoE缺陷小鼠24周。与对照剂相比，ARB、ACEI和ARB + ACEI可显著减少主动脉粥样硬化病变形成（p < 0.05），降低主动脉周围组织单核细胞趋化蛋白-1的表达（p < 0.01）。在这些低剂量的治疗中，血压和心率都没有改变。咪咪普利显著降低动脉粥样硬化组织的脂质沉积和纤溶酶原激活物抑制剂-1在表皮周围组织的表达（p < 0.05）。吡咪普利和联合治疗可显著降低巨噬细胞对动脉粥样硬化斑块的浸润（p < 0.05）。治疗后12周，各治疗组均能降低表皮周围组织中巨噬细胞的聚集（p < 0.05）。这些结果表明，抑制肾素-血管紧张素系统可减轻膜周围炎症并减少动脉粥样硬化病变的形成。(C) 2009 Elsevier Masson SAS。版权所有。
Recent evidence indicates that renin-angiotensin system (RAS) plays an important role in the pathogenesis of atherosclerosis. It was reported that inhibition of RAS with angiotensin II type I receptor blockers (ARBs) or angiotensin converting enzyme inhibitors (ACEIs) is effective in prevention of atherosclerosis. Here, we investigated the effects of an ARB or/and an ACEI on atherosclerosis development and periadventitial inflammation in apolipoprotein E (ApoE)-deficient mice. RT-PCR revealed that major RAS components were expressed in periaortic tissue. Ang II infusion significantly increased accumulation of bone marrow derived cells into both neointima (p < 0.05) and periaortic tissue (p < 0.01). Male ApoE- deficient mice were treated with either vehicle, TA606A (10 mg/kg/day, ARB), imidapril Q mg/kg/day, ACEI) or TA606A plus imidapril (TA606A 10 mg/kg/day + imidapril 3 mg/kg/day, ARB + ACEI) for 24 weeks starting at 12 weeks of age. ARB, ACEI, and ARB + ACEI significantly reduced atherosclerotic lesion formation in aorta compared with vehicle (p < 0.05), with reduced expression of monocyte chemoattractant protein-1 in periaortic tissues (p < 0.01). Neither blood pressure nor heart rate was changed by the treatments at these lower doses. Imidapril significantly reduced lipid deposition in atheroma and plasminogen activator inhibitor-1 expression in periadventitial tissue (p < 0.05, respectively). Imidapril and combination therapy significantly attenuated macrophage infiltration into the atherosclerotic plaque (p < 0.05, respectively). All treatments reduced macrophage accumulation in the periadventitial tissue 12 weeks after treatment (p < 0.05, respectively). These results suggest that inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation. (C) 2009 Elsevier Masson SAS. All rights reserved.