Infection and inflammation induce LDL oxidation in vivo
Infection and inflammation induce LDL oxidation in vivo
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DOI：
10.1161/01.atv.20.6.1536
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发表时间：
2000-06-01
影响因子：
8.7
通讯作者：
Grunfeld, C
中科院分区：
文献类型：
--
作者：
Memon, RA;Staprans, I;Grunfeld, C
流行病学研究表明，慢性感染和炎症性疾病患者的冠状动脉疾病发病率增加。由于脂蛋白的氧化修饰在动脉粥样硬化中起着重要作用，本研究旨在验证宿主对感染和炎症的反应诱导体内脂蛋白氧化的假设。在3种不同的感染和炎症模型中测量脂蛋白氧化，分别用细菌脂多糖（LPS）、酵母聚糖或姜黄素注射叙利亚仓鼠以模拟急性感染、急性全身性炎症和急性局部炎症。通过测定共轭二烯、硫代巴比妥酸反应性物质和脂质过氧化氢的水平，测定血清和脂蛋白组分中氧化脂肪酸的水平。我们的结果表明，在所有3种模型中，血清中共轭二烯和硫代巴比妥酸反应性物质显著增加。此外，LPS和酵母多糖产生4倍至6倍的增加共轭二烯和脂质过氧化氢水平的LDL馏分。LPS也产生了17倍的增加，在LDL的氧化修饰过程中形成的溶血磷脂酰胆碱的LDL含量，最后，从动物中分离的LDL与LPS处理的显着更容易离体氧化铜比从盐水处理的动物中分离的LDL，和3倍的减少发生在氧化的滞后期。这些结果表明，宿主对感染和炎症的反应增加了血清中的氧化脂质，并诱导体内LDL氧化。感染和炎症过程中LDL氧化增加可能促进动脉粥样硬化形成，可能是慢性感染和炎症性疾病患者冠状动脉疾病发病率增加的机制。
Epidemiological studies have shown an increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders. Because oxidative modification of lipoproteins plays a major role in atherosclerosis, the present study was designed to test the hypothesis that the host response to infection and inflammation induces lipoprotein oxidation in vivo. Lipoprotein oxidation was measured in 3 distinct models of infection and inflammation, Syrian hamsters were injected with bacterial lipopolysaccharide (LPS), zymosan, or turpentine to mimic acute infection, acute systemic inflammation, and acute localized inflammation, respectively. Levels of oxidized fatty acids in serum and lipoprotein fractions were measured by determining levels of conjugated dienes, thiobarbituric acid-reactive substances, and lipid hydroperoxides, Our results demonstrate a significant increase in conjugated dienes and thiobarbituric acid-reactive substances in serum in all 3 models. Moreover, LPS and zymosan produced a 4-fold to 6-fold increase in conjugated diene and lipid hydroperoxide levels in LDL fraction. LPS also produced a 17-fold increase in LDL content of lysophosphatidylcholine that is formed during the oxidative modification of LDL, Finally, LDL isolated from animals treated with LPS was significantly more susceptible to ex vivo oxidation with copper than LDL isolated from saline-treated animals, and a 3-fold decrease occurred in the lag phase of oxidation. These results demonstrate that the host response to infection and inflammation increases oxidized lipids in serum and induces LDL oxidation in vivo. Increased LDL oxidation during infection and inflammation may promote atherogenesis and could be a mechanism for increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders.