Sun Qinghua, Wang Aixia, Jin Ximei, Natanzon Alex, Duquaine Damon, Brook Robert D, Aguinaldo Juan-Gilberto S, Fayad Zahi A, Fuster Valentin, Lippmann Morton, Chen Lung Chi, Rajagopalan Sanjay
The Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
JAMA. 2005 Dec 21;294(23):3003-10. doi: 10.1001/jama.294.23.3003.
Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined.
To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model.
DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months.
Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes.
In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001).
In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.
近期研究表明，城市地区吸入颗粒物暴露与心血管事件易感性之间存在联系；然而，确切机制仍有待确定。
在一个易感疾病模型中，检验以下假设：亚慢性暴露于环境相关颗粒物，即使是低浓度，也会加剧动脉粥样硬化并改变血管舒缩张力。
设计、地点和参与者：2004年7月21日至2005年1月12日期间，28只载脂蛋白E基因敲除（apoE-/-）小鼠根据随机分组，分别喂食普通饲料或高脂饲料，并在纽约州塔克斯多每天暴露于浓度小于2.5微米的环境颗粒物（PM2.5）或过滤空气（FA）中6小时，每周5天，共6个月。
胸主动脉和腹主动脉的复合动脉粥样硬化斑块以及血管舒缩张力变化。
在高脂饲料组中，PM2.5组与FA组的平均（标准差）复合斑块面积分别为41.5%（9.8%）和26.2%（8.6%）（P<0.001）；在普通饲料组中，复合斑块面积分别为19.2%（13.1%）和13.2%（8.1%）（P = 0.15）。用油红-O染色法测量主动脉弓中的脂质含量，结果显示，喂食高脂饲料并暴露于PM2.5的小鼠与暴露于FA的小鼠相比，脂质含量增加了1.5倍（分别为30.0 [8.2]和20.0 [7.0]；95%置信区间[CI]，1.21 - 1.83；P = 0.02）。与暴露于FA相比，喂食高脂饲料并暴露于PM2.5的小鼠胸主动脉对去氧肾上腺素和5-羟色胺刺激的血管收缩反应增强（去氧肾上腺素的平均[标准误]，分别为134.2% [5.2%]和100.9% [2.9%]；5-羟色胺的平均[标准误]，分别为156.0% [5.6%]和125.1% [7.5%]；两者P = 0.03）；对内皮依赖性激动剂乙酰胆碱的舒张反应减弱（舒张半最大剂量的平均[标准误]，分别为8.9 [0.2]×10⁻⁸和4.3 [0.1]×10⁻⁸；P = 0.04）。喂食高脂饲料并暴露于PM2.5的小鼠巨噬细胞浸润显著增加，诱导型一氧化氮合酶表达增加，活性氧生成增加，蛋白质硝化产物3-硝基酪氨酸的免疫染色更强（所有P<0.001）。
在apoE-/-小鼠模型中，长期暴露于低浓度PM2.5会改变血管舒缩张力，诱发血管炎症，并加剧动脉粥样硬化。
