Long-term inhalation exposure to nickel nanoparticles exacerbated atherosclerosis in a susceptible mouse model.
Long-term inhalation exposure to nickel nanoparticles exacerbated atherosclerosis in a susceptible mouse model.
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DOI：
10.1289/ehp.1002508
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发表时间：
2011-02
影响因子：
10.4
通讯作者：
Chen LC
中科院分区：
文献类型：
--
作者：
Kang GS;Gillespie PA;Gunnison A;Moreira AL;Tchou-Wong KM;Chen LC
由于已有报道称吸入环境中的超细颗粒物与心肺疾病风险增加之间存在关联，因此有人建议吸入工程纳米颗粒(NPs)也可能对心血管系统产生不利影响。我们利用敏感的小鼠模型研究了吸入氢氧化镍纳米颗粒(Nano-NH)对心血管的长期影响。高脂血症载脂蛋白E缺陷(ApoE−/−)小鼠通过全身吸入系统暴露在0或79μg Ni/m~3的纳米NH中，每天5小时，每周5天，持续1周或5个月。我们测量了肺和心血管组织中氧化应激和炎症的各种指标，并确定了升主动脉上斑块的形成。吸入纳米NH可在肺和肺外器官引起显著的氧化应激和炎症，表现为某些抗氧化酶和炎症细胞因子基因的mRNA水平上调；主动脉线粒体DNA损伤增加；支气管肺泡灌洗液中有明显的炎症迹象；肺组织病理学改变；以及急性时相反应的诱导。此外，在暴露5个月后，纳米NH加剧了载脂蛋白E−/−小鼠动脉粥样硬化的进展。这是第一次报道吸入纳米材料对心血管的长期毒性的研究。我们的结果清楚地表明，长期吸入纳米NH可诱导氧化应激和炎症，不仅在肺部，而且在心血管系统，这种应激和炎症最终可能导致载脂蛋白E−/−小鼠动脉粥样硬化的进展。
Because associations have been reported between inhaled ambient ultrafine particles and increased risk of cardiopulmonary disease, it has been suggested that inhaled engineered nanoparticles (NPs) may also induce adverse effects on the cardiovascular system. We examined the long-term cardiovascular effects of inhaled nickel hydroxide NPs (nano-NH) using a sensitive mouse model. Hyperlipidemic, apoprotein E-deficient (ApoE−/−) mice were exposed to nano-NH at either 0 or 79 μg Ni/m3, via a whole-body inhalation system, for 5 hr/day, 5 days/week, for either 1 week or 5 months. We measured various indicators of oxidative stress and inflammation in the lung and cardiovascular tissue, and we determined plaque formation on the ascending aorta. Inhaled nano-NH induced significant oxidative stress and inflammation in the pulmonary and extrapulmonary organs, indicated by up-regulated mRNA levels of certain antioxidant enzyme and inflammatory cytokine genes; increased mitochondrial DNA damage in the aorta; significant signs of inflammation in bronchoalveolar lavage fluid; changes in lung histopathology; and induction of acute-phase response. In addition, after 5-month exposures, nano-NH exacerbated the progression of atherosclerosis in ApoE−/− mice. This is the first study to report long-term cardiovascular toxicity of an inhaled nanomaterial. Our results clearly demonstrate that long-term exposure to inhaled nano-NH can induce oxidative stress and inflammation, not only in the lung but also in the cardiovascular system, and that this stress and inflammation can ultimately contribute to progression of atherosclerosis in ApoE−/− mice.
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影响因子：
37.8
作者：
Pope, CA;Burnett, RT;Godleski, JJ
通讯作者：
Godleski, JJ
DOI：
10.1016/j.ejvs.2008.11.018
发表时间：
2009-06-01
影响因子：
5.7
作者：
Graebe, M.;Pedersen, S. F.;Kjaer, A.
通讯作者：
Kjaer, A.
DOI：
10.1161/01.atv.14.1.133
发表时间：
1994-01-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
NAKASHIMA, Y;PLUMP, AS;ROSS, R
通讯作者：
ROSS, R
影响因子：
10.4
作者：
Nurkiewicz, Timothy R;Porter, Dale W;Barger, Mark;Millecchia, Lyndell;Rao, K Murali K;Marvar, Paul J;Hubbs, Ann F;Castranova, Vincent;Boegehold, Matthew A
通讯作者：
Boegehold, Matthew A
影响因子：
3.2
作者：
LeBlanc, A. J.;Moseley, A. M.;Chen, B. T.;Frazer, D.;Castranova, V.;Nurkiewicz, T. R.
通讯作者：
Nurkiewicz, T. R.