Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness, inflammation, and collagen deposition in the lung
Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness, inflammation, and collagen deposition in the lung
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DOI：
10.1194/jlr.m004549
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发表时间：
2010-09-01
影响因子：
6.5
通讯作者：
Pritchard, Kirkwood A., Jr.
中科院分区：
文献类型：
--
作者：
Wang, Weiling;Xu, Hao;Pritchard, Kirkwood A., Jr.
高密度脂蛋白与肺功能的关系尚不清楚。为了确定机制关系，我们研究了载脂蛋白A-I （apoA-I）基因缺失对血脂、对氧磷酶（PON1）、促炎HDL （p-HDL）、血管舒张、气道高反应性和肺氧化应激以及炎症的影响。与C57BL/6J小鼠相比，ApoA-I缺失（ApoA-I(/)）小鼠总胆固醇和高密度脂蛋白胆固醇降低，但促炎HDL升高。虽然apoa - 1 -/-小鼠的PON1蛋白升高，但PON1活性降低。apoa - 1缺乏没有改变面部动脉的血管扩张，但改变了肺动脉的舒张反应。中央气道阻力未见改变。然而，由组织阻尼和弹性介导的气道阻力在apoA-I-/-小鼠中增加，呼气末正压（PEEP）研究也证实了这一发现。炎症细胞、胶原沉积、3-硝基酪氨酸和4-羟基-2-壬烯醛在apoA-I（/）肺中增加，但氧化磷脂没有增加。4-羟基-2-壬烯醛与转化生长因子β -1 （TGF β -1）的共定位在apoA-I-/-肺中增加。黄嘌呤氧化酶、髓过氧化物酶和内皮型一氧化氮合酶在apoA-I（/）肺中升高。apoA-I-/-小鼠支气管肺泡灌洗液（BALF）中可检测到二氯二氢荧光素的氧化剂增加。相比之下，apoA-I（/）小鼠的亚硝酸盐+ BALF水平降低。这些数据表明，apoA-I在限制肺部炎症和氧化应激中发挥重要作用，如果不加以预防，将会降低肺动脉血管舒张并增加气道高反应性。-王伟，徐辉，史勇，S. Nandedkar，张宏，高宏，T. Feroah， D. Weihrauch， M. L. Schulte， D. W. Jones， J. Jarzembowski， M. Sorci-Thomas， K. A. Pritchard, Jr.载脂蛋白A-I基因缺失对气道高反应性、炎症和肺胶原沉积的影响。[j] .油脂杂志。2010。51: 2560 - 2570。
The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-inflammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and inflammation. ApoA-I null (apoA-I (/) ) mice had reduced total and HDL cholesterol but increased pro-inflammatory HDL compared with C57BL/6J mice. Although PON1 protein was increased in apoA-I-/- mice, PON1 activity was decreased. ApoA-I deficiency did not alter vasodilatation of facialis arteries, but it did alter relaxation responses of pulmonary arteries. Central airway resistance was unaltered. However, airway resistance mediated by tissue dampening and elastance were increased in apoA-I-/- mice, a finding also confirmed by positive end-expiratory pressure (PEEP) studies. Inflammatory cells, collagen deposition, 3-nitrotyrosine, and 4-hydroxy-2-nonenal were increased in apoA-I (/) lungs but not oxidized phospholipids. Colocalization of 4-hydroxy-2-nonenal with transforming growth factor beta-1 (TGF beta-1 was increased in apoA-I-/- lungs. Xanthine oxidase, myeloperoxidase and endothelial nitric oxide synthase were increased in apoA-I (/) lungs. Dichlorodihydrofluorescein-detectable oxidants were increased in bronchoalveolar lavage fluid (BALF) in apoA-I-/- mice. In contrast, BALF nitrite+nitrate levels were decreased in apoA-I (/) mice. These data demonstrate that apoA-I plays important roles in limiting pulmonary inflammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness.-Wang, W., H. Xu, Y. Shi, S. Nandedkar, H. Zhang, H. Gao, T. Feroah, D. Weihrauch, M. L. Schulte, D. W. Jones, J. Jarzembowski, M. Sorci-Thomas, and K. A. Pritchard, Jr. Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness, inflammation, and collagen deposition in the lung. J. Lipid Res. 2010. 51: 2560-2570.