Short-term 20-mg atorvastatin therapy reduces key inflammatory factors including c-Jun N-terminal kinase and dendritic cells and matrix metalloproteinase expression in human abdominal aortic aneurysmal wall
Short-term 20-mg atorvastatin therapy reduces key inflammatory factors including c-Jun N-terminal kinase and dendritic cells and matrix metalloproteinase expression in human abdominal aortic aneurysmal wall
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DOI：
10.1016/j.atherosclerosis.2009.03.028
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发表时间：
2009-10-01
期刊：
影响因子：
5.3
通讯作者：
Daida, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kajimoto, Kan;Miyauchi, Katsumi;Daida, Hiroyuki
背景：腹主动脉瘤（AAA）具有慢性炎症性疾病和不可逆的结缔组织破坏的特征。最近的一项实验研究确定c-Jun N末端激酶（JNK）作为AAA发病机制中的近端信号分子，血管树突状细胞作为炎症反应和细胞外基质降解的关键参与者。他汀类药物可以抑制细胞增殖和血管炎症，这可能有助于防止AAA进展。然而，缺乏来自人类研究的支持性临床数据。我们假设阿托伐他汀可能抑制JNK和树突状细胞，从而抑制炎性细胞和基质金属蛋白酶（MMPs）在人AAA组织中。方法：AAA患者随机分为阿托伐他汀（20 mg/d，n = 10）和非治疗组（n = 10）。治疗4周后，患者接受腹主动脉置换术，组织标本，并使用免疫组织化学定量图像analysis.Results的组织成分进行评估：阿托伐他汀显着降低JNK（1.1%比8.1%，P = 0.0002）和树突状细胞（3.2比7.2，P = 0.003）的表达与对照组相比。在阿托伐他汀组中，T细胞（142 vs. 315，P = 0.008）、巨噬细胞（13 vs. 24，P = 0.048）以及MMP-2（7.8% vs. 21%，P = 0.049）和MMP-9（13% vs. 24%，P = 0.028）的免疫反应性也受到抑制。血清低密度脂蛋白胆固醇水平下降了40%，在阿托伐他汀group.Conclusions：阿托伐他汀治疗急性减少JNK的表达和树突状细胞，导致减少炎性细胞含量和基质金属蛋白酶在AAA壁的表达。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Background: Abdominal aortic aneurysm(AAA) accumulates features of a chronic inflammatory disorder and irreversible destruction of connective tissue. A recent experimental study identified c-Jun N terminal kinase (JNK) as a proximal signaling molecule in the pathogenesis of AAA and vascular dendritic cells as key players in the inflammatory reaction and degradation of the extracellular matrix. Statins can inhibit cell proliferation and vascular inflammation, which might help prevent AAA progression. However, supporting clinical data from human studies are lacking. We hypothesized that atorvastatin might inhibit JNK and dendritic cells, resulting in suppression of inflammatory cells and matrix metalloproteinases (MMPs) in human tissue of AAA.Methods: Patients with AAA were randomized to atorvastatin (20 mg/day, n = 10) and non-treated (n = 10) groups. After treatment for 4 weeks, patients underwent abdominal aorta replacement, tissue specimens were obtained, and tissue composition was assessed using immunohistochemistry with quantitative image analysis.Results: Atorvastatin significantly reduced expression of JNK (1.1% vs. 8.1%, P = 0.0002) and dendritic cells (3.2 vs. 7.2, P = 0.003) compared to controls. T cells (142 vs. 315, P = 0.008), macrophages (13 vs. 24, P = 0.048) and immunoreactivity to MMP-2 (7.8% vs. 21%, P = 0.049) and MMP-9 (13% vs. 24%, P = 0.028) were also suppressed in the atorvastatin group. Serum low-density lipoprotein cholesterol level was decreased by 40% in the atorvastatin group.Conclusions: Atorvastatin treatment acutely reduces JNK expression and dendritic cells, resulting in reduced inflammatory cell content and expression of MMPs in the AAA wall. (C) 2009 Elsevier Ireland Ltd. All rights reserved.