Dioxin exposure is an environmental risk factor for ischemic heart disease.
Dioxin exposure is an environmental risk factor for ischemic heart disease.
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DOI：
10.1385/ct:1:4:285
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发表时间：
2001-01-01
影响因子：
3.2
通讯作者：
Puga, A
中科院分区：
文献类型：
--
作者：
Dalton, T P;Kerzee, J K;Puga, A
流行病学研究已将二恶英暴露与缺血性心脏病引起的死亡率增加联系起来。为了验证二恶英暴露可能构成动脉粥样硬化环境危险因素的假设，我们将C57BL/6J小鼠每天暴露于5微克/千克的二恶英中3天，并测量了心脏病的各种分子和生理标志物。二恶英治疗导致尿中血管活性类二十烷醇排泄增加和平均尾袖血压升高。此外，在Apoe（+/+）小鼠和高脂血症Apoe（-/-）小鼠中，二恶英暴露导致甘油三酯增加，但高密度脂蛋白没有增加。二恶英暴露也导致Apoe（-/-）小鼠低密度脂蛋白增加。治疗后，二恶英与低密度脂蛋白颗粒相关，这可能是将化合物递送到动脉粥样硬化斑块的载体。二恶英对C57Bl/6J小鼠血管平滑肌细胞的处理导致与细胞增殖和凋亡有关的几个基因的失调。用二恶英（150 ng/kg，每周3次）亚慢性治疗Apoe（-/-）小鼠7或26周后，与对照组小鼠相比，其动脉粥样硬化病变发病更早，严重程度更高。这些结果表明，二恶英可能通过加重缺血性心脏病的严重程度而增加其发病率。
Epidemiologic studies have linked dioxin exposure to increased mortality caused by ischemic heart disease. To test the hypothesis that dioxin exposure may constitute an environmental risk factor for atherosclerosis, we exposed C57BL/6J mice to 5 microg/kg of dioxin daily for 3 d, and measured various molecular and physiological markers of heart disease. Dioxin treatment led to an increase in the urinary excretion of vasoactive eicosanoids and an elevation in the mean tail-cuff blood pressure. In addition, dioxin exposure led to an increase in triglycerides, but not in high-density lipoproteins, in both Apoe(+/+) mice and in hyperlipidemic Apoe(-/- mice. Dioxin exposure also led to an increase in low-density lipoproteins in Apoe(-/-) mice. After treatment, dioxin was associated with low-density lipoprotein particles, which might serve as a vehicle to deliver the compound to atherosclerotic plaques. Dioxin treatment of vascular smooth-muscle cells taken from C57Bl/6J mice resulted in the deregulation of several genes involved in cell proliferation and apoptosis. Subchronic treatment of Apoe(-/-) mice with dioxin (150 ng/kg, three times weekly) for 7 or 26 wk caused a trend toward earlier onset and greater severity of atherosclerotic lesions compared to those of vehicle treated mice. These results suggest that dioxin may increase the incidence of ischemic heart disease by exacerbating its severity.