Xu Xiaohua, Kherada Nisharahmed, Hong Xinru, Quan Chunli, Zheng Ling, Wang Aixia, Wold Loren E, Lippmann Morton, Chen Lung Chi, Rajagopalan Sanjay, Sun Qinghua
Division of Environmental Health Sciences, Colleges of Medicine and Public Health, The Ohio State University, Columbus, OH 43210-1240, USA.
Toxicol Lett. 2009 Dec 1;191(1):57-68. doi: 10.1016/j.toxlet.2009.08.006. Epub 2009 Aug 14.
Our aim was to test the hypothesis that exposure to whole diesel exhaust (WDE) would enhance angiogenesis/vasculogenesis. Male apolipoprotein E-deficient mice, with either scaffold implantation subcutaneously or hindlimb ischemia, were exposed to either WDE (containing diesel exhaust particle [DEP] at a concentration of about 1mg/m(3)) or filtered air 6 h/day, 5 days/week in a whole body exposure chamber for 2, 5, or 8 weeks, respectively. WDE exposure significantly increased total cell counts in the scaffolds, aortic, and perivascular fat tissues. Macrophage infiltration was enhanced and CD31 expression increased in the scaffolds, which was coupled by increased alpha-smooth muscle actin (alpha-SMA) expression. WDE exposure led to increased CD31 expression, while decreasing endothelial nitric oxide synthase in the aortic wall. The vessel volume measured by micro-CT was increased in ischemic and non-ischemic hindlimbs in response to WDE exposure. DEP exposure induced capillary-like tube formation in endothelial cells in vitro, and caused capillary sprouting from aortic rings ex vivo. In addition, WDE exposure significantly increased mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, while decreasing prolylhydroxylase (PHD) 2 expression. WDE exposure increases inflammatory cell infiltration, enhances the vessel volume/flow, and increases capillary tube formation and sprouting, thereby inducing angiogenesis and vasculogenesis. The angiogenic effects may occur through increasing HIF-1alpha and VEGF while decreasing PHD2 expression.
我们的目的是验证暴露于全柴油废气（WDE）会增强血管生成/血管发生这一假设。将载脂蛋白E缺乏的雄性小鼠，分别进行皮下支架植入或后肢缺血处理，然后将其置于全身暴露舱中，每天暴露于WDE（含浓度约为1mg/m³的柴油废气颗粒[DEP]）或过滤空气中6小时，每周5天，分别持续2周、5周或8周。暴露于WDE显著增加了支架、主动脉和血管周围脂肪组织中的总细胞计数。支架中的巨噬细胞浸润增强，CD31表达增加，同时α平滑肌肌动蛋白（α-SMA）表达也增加。WDE暴露导致主动脉壁中CD31表达增加，而内皮型一氧化氮合酶减少。通过微型CT测量的血管体积在缺血和非缺血后肢中因WDE暴露而增加。DEP暴露在体外诱导内皮细胞形成毛细血管样管，并在离体条件下导致主动脉环出现毛细血管芽生。此外，WDE暴露显著增加血管内皮生长因子（VEGF）和缺氧诱导因子（HIF）-1α的mRNA表达，同时降低脯氨酰羟化酶（PHD）2的表达。WDE暴露增加炎症细胞浸润，增强血管体积/血流量，并增加毛细血管管形成和芽生，从而诱导血管生成和血管发生。血管生成作用可能通过增加HIF-1α和VEGF同时降低PHD2表达而发生。
