Department of Pharmaceutical Sciences, The University of New Mexico, College of Pharmacy, Albuquerque, NM, USA.
Biosciences Division, Los Alamos National Laboratories, Los Alamos, NM, USA.
Cardiovasc Toxicol. 2020 Jun;20(3):211-221. doi: 10.1007/s12012-019-09546-5.
Roadside proximity and exposure to mixed vehicular emissions (MVE) have been linked to adverse pulmonary and vascular outcomes. However, because of the complex nature of the contribution of particulate matter (PM) versus gases, it is difficult to decipher the precise causative factors regarding PM and the copollutant gaseous fraction. To this end, C57BL/6 and apolipoprotein E knockout mice (ApoE) were exposed to either filtered air (FA), fine particulate (FP), FP+gases (FP+G), ultrafine particulate (UFP), or UFP+gases (UFP+G). Two different timeframes were employed: 1-day (acute) or 30-day (subchronic) exposures. Examined biological endpoints included aortic vasoreactivity, aortic lesion quantification, and aortic mRNA expression. Impairments in vasorelaxation were observed following acute exposure to FP+G in C57BL/6 animals and FP, UFP, and UFP+G in ApoE animals. These effects were completely abrogated or markedly reduced following subchronic exposure. Aortic lesion quantification in ApoE animals indicated a significant increase in atheroma size in the UFP-, FP-, and FP+G-exposed groups. Additionally, ApoE mice demonstrated a significant fold increase in TNFα expression following FP+G exposure and ET-1 following UFP exposure. Interestingly, C57BL/6 aortic gene expression varied widely across exposure groups. TNFα decreased significantly following FP exposure and CCL-5 decreased in the UFP-, FP-, and FP+G-exposed groups. Conversely, ET-1, CCL-2, and CXCL-1 were all significantly upregulated in the FP+G group. These findings suggest that gas-particle interactions may play a role in vascular toxicity, but the contribution of surface area is not clear.
路边接近度和混合机动车排放（MVE）的暴露与肺部和血管不良后果有关。然而，由于颗粒物（PM）与气体的贡献的复杂性，很难确定 PM 和共污染物气体部分的确切致病因素。为此，C57BL/6 和载脂蛋白 E 敲除小鼠（ApoE）分别暴露于过滤空气（FA）、细颗粒物（FP）、FP+气体（FP+G）、超细颗粒物（UFP）或 UFP+气体（UFP+G）。采用了两种不同的时间框架：1 天（急性）或 30 天（亚慢性）暴露。检查的生物学终点包括主动脉血管反应性、主动脉病变定量和主动脉 mRNA 表达。急性暴露于 FP+G 的 C57BL/6 动物和 FP、UFP 和 UFP+G 的 ApoE 动物观察到血管舒张功能受损。亚慢性暴露后，这些影响完全消除或显著减少。ApoE 动物的主动脉病变定量表明，UFP、FP 和 FP+G 暴露组的动脉粥样硬化大小显著增加。此外，ApoE 小鼠在 FP+G 暴露后 TNFα 表达显著增加，在 UFP 暴露后 ET-1 表达显著增加。有趣的是，C57BL/6 主动脉基因表达在暴露组之间差异很大。FP 暴露后 TNFα 显著下降，UFP、FP 和 FP+G 暴露组 CCL-5 下降。相反，FP+G 组 ET-1、CCL-2 和 CXCL-1 均显著上调。这些发现表明，气粒相互作用可能在血管毒性中起作用，但表面积的贡献尚不清楚。
