Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy
Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy
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DOI：
10.1016/j.cardiores.2006.11.031
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发表时间：
2007-02-01
影响因子：
10.8
通讯作者：
Kolattukudy, Pappachan E.
中科院分区：
文献类型：
--
作者：
Niu, Jianli;Azfer, Asim;Kolattukudy, Pappachan E.
目的：氧化铈（CeO 2）纳米颗粒已被证明可以保护培养中的细胞免受致死性应激，但没有体内保护的报道。小鼠心脏特异性表达单核细胞趋化蛋白（MCP）-1导致与内质网（ER）应激激活相关的缺血性心肌病。本研究的目的是评估CeO 2纳米颗粒对心脏功能和重塑以及ER应激反应在这一小鼠模型cardiomy.Methods：MCP-1转基因小鼠（MCP小鼠）和野生型对照静脉注射15 nmol的CeO 2纳米颗粒或车辆只有每周两次，2周。心功能，心肌组织学，硝基酪氨酸的形成，细胞因子的表达，和ER应激相关基因进行了evaluated.Results：治疗与CeO 2纳米粒子显着抑制进行性左心室功能障碍和扩张MCP小鼠，并引起MCP-1，C-反应蛋白，总硝化蛋白的血清水平显着下降。CeO 2纳米颗粒显著抑制了心肌中单核细胞/巨噬细胞的浸润、3-硝基酪氨酸的蓄积、凋亡性细胞死亡以及促炎性细胞因子、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1 β和IL-6的表达。关键ER应激相关基因的表达，包括葡萄糖调节蛋白78（Grp 78）、蛋白质二硫键异构酶（PDI）和热休克蛋白（HSP 25、HSP 40、HSP 70）也被CeO 2纳米颗粒抑制。CeO 2纳米颗粒通过减弱心肌氧化应激，ER应激，和炎症过程可能通过其自身再生的抗氧化特性。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Cerium oxide (CeO2) nanoparticles have been shown to protect cells in culture from lethal stress, but no protection in vivo has been reported. Cardiac-specific expression of monocyte chemoattractant protein (MCP)-1 in mice causes ischemic cardiomyopathy associated with activation of endoplasmic reticulum (ER) stress. The aim of this study was to assess the effects of CeO2 nanoparticles on cardiac function and remodeling as well as ER stress response in this murine model of cardiomyopathy.Methods: MCP-1 transgenic mice (MCP mice) and wild-type controls were administered intravenously 15 nmol of CeO2 nanoparticles or vehicle only twice a week for 2 weeks. Cardiac function, myocardial histology, nitrotyrosine formation, expression of cytokines, and ER stress-associated genes were evaluated.Results: Treatment with CeO2 nanoparticles markedly inhibited progressive left ventricular dysfunction and dilatation in MCP mice and caused a significant decrease in serum levels of MCP-1, C-reactive protein, and total nitrated proteins. The infiltration of monocytes/macrophages, accumulation of 3-nitrotyrosine, apoptotic cell death, and expression of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 in the myocardium were markedly inhibited by CeO2 nanoparticles. Expression of the key ER stress-associated genes, including glucose-regulated protein 78 (Grp78), protein disulfide isomerase (PDI), and heat shock proteins (HSP25, HSP40, HSP70), were also suppressed by CeO2 nanoparticles.Conclusions: CeO2 nanoparticles protect against the progression of cardiac dysfunction and remodeling by attenuation of myocardial oxidative stress, ER stress, and inflammatory processes probably through their autoregenerative antioxidant properties. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.