Psoriasis alters HDL composition and cholesterol efflux capacity

Psoriasis alters HDL composition and cholesterol efflux capacity
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DOI:
10.1194/jlr.m027367
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发表时间:
2012-08-01
影响因子:
6.5
通讯作者:
Marsche, Gunther
Marsche, Gunther
中科院分区:
生物学2区
文献类型:
--
作者:
Holzer, Michael;Wolf, Peter;Marsche, Gunther

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牛皮癣是一种慢性炎症性皮肤病,与心肌梗死和中风的增加有关。高密度脂蛋白功能受损可能是银屑病患者心血管死亡率过高的原因之一。然而,关于银屑病对HDL组成和功能的影响的数据有限。从银屑病患者和健康对照者中分离HDL,采用超离心和鸟枪蛋白质组学方法,并采用生化方法监测HDL组成的变化。我们观察到银屑病患者HDL的apoA-I水平显著降低,而apoA-II和参与急性期反应、免疫反应和内肽酶/蛋白酶抑制的蛋白质水平升高。银屑病HDL含有减少的磷脂和胆固醇。就功能而言,这些成分的改变损害了银屑病HDL促进巨噬细胞胆固醇流出的能力。重要的是,HDL-胆固醇流出能力与银屑病面积和严重程度指数呈负相关。我们观察到,对照HDL,以及银屑病HDL,抑制二氢罗丹明(DHR)氧化到类似的程度,这表明银屑病HDL的抗氧化活性没有显着改变。(jlr)观察表明,在银屑病HDL中观察到的组成改变反映了向损害HDL的胆固醇流出能力的促炎性特征的转变,并可能提供银屑病和心血管疾病之间的联系。Holzer,M.,P. Wolf,S.库尔契奇河Birner-Gruenberger,W. Weger,M. Inzinger,D.贾迈勒角Wadsack,A. Heinemann和G.马舍银屑病改变HDL组成和胆固醇流出能力。J. Lipid Res. 2012. 53:1618-1624。
Psoriasis, a chronic inflammatory skin disease, has been linked to increased myocardial infarction and stroke. Functional impairment of HDL may contribute to the excess cardiovascular mortality of psoriatic patients. However, data available regarding the impact of psoriasis on HDL composition and function are limited. HDL from psoriasis patients and healthy controls was isolated by ultracentrifugation and shotgun proteomics, and biochemical methods were used to monitor changed HDL composition. We observed a significant reduction in apoA-I levels of HDL from psoriatic patients, whereas levels of apoA-II and proteins involved in acute-phase response, immune response, and endopeptidase/protease inhibition were increased. Psoriatic HDL contained reduced phospholipid and cholesterol. With regard to function, these compositional alterations impaired the ability of psoriatic HDL to promote cholesterol efflux from macrophages. Importantly, HDL-cholesterol efflux capability negatively correlated with psoriasis area and severity index. We observed that control HDL, as well as psoriatic HDL, inhibited dihydrorhodamine (DHR) oxidation to a similar extent, suggesting that the anti-oxidative activity of psoriatic HDL is not significantly altered.(jlr) observations suggest that the compositional alterations observed in psoriatic HDL reflect a shift to a proinflammatory profile that impairs cholesterol efflux capacity of HDL and may provide a link between psoriasis and cardiovascular disease.-Holzer, M., P. Wolf, S. Curcic, R. Birner-Gruenberger, W. Weger, M. Inzinger, D. El-Gamal, C. Wadsack, A. Heinemann, and G. Marsche. Psoriasis alters HDL composition and cholesterol efflux capacity. J. Lipid Res. 2012. 53: 1618-1624.