Feingold Kenneth R, Shigenaga Judy K, Chui Lisa G, Moser Arthur, Khovidhunkit Weerapan, Grunfeld Carl
Department of Veterans Affairs Medical Center, Metabolism Section, SFVAMC, San Francisco, CA 94121, United States.
Atherosclerosis. 2008 Jul;199(1):19-26. doi: 10.1016/j.atherosclerosis.2007.10.007. Epub 2007 Dec 3.
Inflammation can produce abnormalities that could increase the risk for atherosclerosis including alterations in lipid and lipoprotein metabolism. Apolipoprotein M is a recently described HDL-associated apoprotein expressed mainly in the liver and kidney with protective effects against atherosclerosis. In this study, we describe the regulation of apolipoprotein M during the acute phase response. Stimuli that produce systemic inflammation, LPS, zymosan, or turpentine, decrease apolipoprotein M mRNA levels in the liver and kidney. Treatment of Hep3B hepatoma cells with TNF or IL-1 also decreased apolipoprotein M mRNA levels. The decrease in apolipoprotein M mRNA leads to a decrease in apolipoprotein M secretion into the media in Hep3B cells and a decrease in mouse serum following LPS administration. Moreover, in humans with acute bacterial infections or chronic HIV infection, serum apolipoprotein M levels are decreased. Apolipoprotein M is a negative acute response protein that decreases during infection and inflammation. These results are consistent with the finding that infections and inflammatory disorders accompanied by systemic inflammation are associated with an increased risk of atherosclerosis.
炎症可产生一些异常情况，这些异常可能会增加动脉粥样硬化的风险，包括脂质和脂蛋白代谢的改变。载脂蛋白M是一种最近被描述的与高密度脂蛋白相关的载脂蛋白，主要在肝脏和肾脏中表达，对动脉粥样硬化具有保护作用。在本研究中，我们描述了急性期反应期间载脂蛋白M的调节情况。能引起全身炎症的刺激物，如脂多糖、酵母聚糖或松节油，会降低肝脏和肾脏中载脂蛋白M的mRNA水平。用肿瘤坏死因子或白细胞介素-1处理Hep3B肝癌细胞也会降低载脂蛋白M的mRNA水平。载脂蛋白M的mRNA水平降低导致Hep3B细胞中载脂蛋白M分泌到培养基中的量减少，以及脂多糖给药后小鼠血清中载脂蛋白M水平降低。此外，在患有急性细菌感染或慢性HIV感染的人类中，血清载脂蛋白M水平会降低。载脂蛋白M是一种负急性期反应蛋白，在感染和炎症期间会减少。这些结果与以下发现一致，即伴有全身炎症的感染和炎症性疾病与动脉粥样硬化风险增加有关。
