Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice
Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice
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DOI：
10.1194/jlr.m035014
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发表时间：
2013-06-01
影响因子：
6.5
通讯作者：
Hsiai, Tzung
中科院分区：
文献类型：
--
作者：
Li, Rongsong;Navab, Mohamad;Hsiai, Tzung
暴露在环境颗粒物(PM)中是心血管疾病的危险因素。氧化还原活性超细颗粒(UFP)可促进血管氧化应激和炎症反应。我们假设UFP调节高密度脂蛋白的脂代谢和抗氧化能力，这与动脉粥样硬化病变的大小有关。低密度脂蛋白受体缺失型(LDLR-/-)小鼠暴露于过滤空气(FA)或超滤膜(UFP)中10周，同时或不给予由D-氨基酸组成的载脂蛋白A-I模拟肽D-4F。暴露于超低密度脂蛋白的LDLR-/-小鼠出现血浆高密度脂蛋白水平(P<；0.01)、对氧磷酶活性(P<；0.01)和高密度脂蛋白抗氧化能力(P<；0.05)降低，但低密度脂蛋白氧化、游离氧化脂肪酸、甘油三酯、血清淀粉样蛋白A(P<；0.05)和肿瘤坏死因子α(P<；0.05)增加，同时主动脉面染色的动脉粥样硬化病变率增加62%，主动脉窦横断面病变面积增加220%(P<；0.001)。D-4F给药可显著减轻上述变化。在脂肪喂养的LDLR-/-小鼠中，UFP暴露促进了促动脉粥样硬化的脂质代谢，降低了高密度脂蛋白的抗氧化能力，与暴露于FA的动物相比，与之相关的是动脉粥样硬化病变范围更大。D-4F可减弱UFP介导的促动脉粥样硬化作用，提示脂质氧化在UFP介导的动脉粥样硬化中所起的作用。
Exposure to ambient particulate matter (PM) is a risk factor for cardiovascular diseases. The redox-active ultrafine particles (UFPs) promote vascular oxidative stress and inflammatory responses. We hypothesized that UFPs modulated lipid metabolism and anti-oxidant capacity of high density lipoprotein (HDL) with an implication in atherosclerotic lesion size. Fat-fed low density lipoprotein receptor-null (LDLR-/-) mice were exposed to filtered air (FA) or UFPs for 10 weeks with or without administering an apolipoprotein A-I mimetic peptide made of D-amino acids, D-4F. LDLR-/- mice exposed to UFPs developed a reduced plasma HDL level (P < 0.01), paraoxonase activity (P < 0.01), and HDL anti-oxidant capacity (P < 0.05); but increased LDL oxidation, free oxidized fatty acids, triglycerides, serum amyloid A (P < 0.05), and tumor necrosis factor alpha (P < 0.05), accompanied by a 62% increase in the atherosclerotic lesion ratio of the en face aortic staining and a 220% increase in the cross-sectional lesion area of the aortic sinus (P < 0.001). D-4F administration significantly attenuated these changes. UFP exposure promoted pro-atherogenic lipid metabolism and reduced HDL anti-oxidant capacity in fat-fed LDLR-/- mice, associated with a greater atherosclerotic lesion size compared with FA-exposed animals. D-4F attenuated UFP-mediated pro-atherogenic effects, suggesting the role of lipid oxidation underlying UFP-mediated atherosclerosis.