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Dysfunctional high-density lipoproteins have distinct composition diminished anti-inflammatory potential and discriminate acute coronary syndrome from stable coronary artery disease patients

机译:功能异常的高密度脂蛋白具有独特的成分消炎潜力降低并与稳定的冠心病患者区别开急性冠状动脉综合征

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摘要

There is a stringent need to find means for risk stratification of coronary artery diseases (CAD) patients. We aimed at identifying alterations of plasma high-density lipoproteins (HDL) components and their validation as dysfunctional HDL that could discriminate between acute coronary syndrome (ACS) and stable angina (SA) patients. HDL2 and HDL3 were isolated from CAD patients’ plasma and healthy subjects. ApolipoproteinAI (apoAI), apoAII, apoCIII, malondialdehyde (MDA), myeloperoxidase (MPO), ceruloplasmin and paraoxonase1 (PON1) were assessed. The anti-inflammatory potential of HDL subfractions was tested by evaluating the secreted inflammatory molecules of tumor necrosis factor α-activated endothelial cells (EC) upon co-incubation with HDL2 or HDL3. We found in ACS versus SA patients: 40% increased MPO, MDA, apoCIII in HDL2 and HDL3, 35% augmented apoAII in HDL2, and in HDL3 increased ceruloplasmin, decreased apoAII (40%) and PON1 protein and activity (15% and 25%). Co-incubation of activated EC with HDL2 or HDL3 from CAD patients induced significantly increased levels of secreted inflammatory molecules, 15–20% more for ACS versus SA. In conclusion, the assessed panel of markers correlates with the reduced anti-inflammatory potential of HDL subfractions isolated from ACS and SA patients (mostly for HDL3 from ACS) and can discriminate between these two groups of CAD patients.
机译:迫切需要找到对冠心病(CAD)患者进行风险分层的方法。我们旨在鉴定血浆高密度脂蛋白(HDL)成分的变化,并将其确认为功能异常的HDL,以区分急性冠状动脉综合征(ACS)和稳定型心绞痛(SA)患者。 HDL2和HDL3是从CAD患者的血浆和健康受试者中分离出来的。评估了载脂蛋白AI(apoAI),apoAII,apoCIII,丙二醛(MDA),髓过氧化物酶(MPO),铜蓝蛋白和对氧磷酶1(PON1)。通过与HDL2或HDL3共孵育后,通过评估肿瘤坏死因子α激活的内皮细胞(EC)分泌的炎症分子来测试HDL亚组分的抗炎潜力。我们在ACS和SA患者中发现:HDL2和HDL3中MPO,MDA,apoCIII增加40%,HDL2中apoAII增加35%,HDL3中铜蓝蛋白增加,apoAII(40%)和PON1蛋白和活性降低(15%和25 %)。来自CAD患者的活化EC与HDL2或HDL3共同孵育可诱导分泌的炎症分子水平显着增加,ACS较SA多15-20%。总之,所评估的标志物组与从ACS和SA患者中分离出的HDL亚组分(主要是从ACS获得的HDL3)的抗炎潜力降低相关,并且可以区分这两组CAD患者。

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