Alwaili Khalid, Bailey Dana, Awan Zuhier, Bailey Swneke D, Ruel Isabelle, Hafiane Anouar, Krimbou Larbi, Laboissiere Sylvie, Genest Jacques
McGill University Health Centre, Division of Cardiology, Montreal, Quebec, Canada.
Biochim Biophys Acta. 2012 Mar;1821(3):405-15. doi: 10.1016/j.bbalip.2011.07.013. Epub 2011 Jul 23.
Inflammation is a major factor underlying acute coronary syndromes (ACS). HDL particles may be remodeled, becoming functionally defective, under the inflammatory conditions seen in ACS. Shotgun proteomics was used to monitor changes in the HDL proteome between male age-matched control, stable CAD, and ACS subjects (n=10/group). HDL was isolated by ultracentrifugation and separated by 1D-gel followed by LC-MS/MS. We identified 67 HDL-associated proteins, 20 of which validated recently identified proteins including vitronectin and complement C4B, and 5 of which were novel. Using gene ontology analysis, we found that the HDL-proteome consisted of proteins involved in cholesterol homeostasis (~50%), with significant contributions by proteins involved in lipid binding, antioxidant, acute-phase response, immune response, and endopeptidase/protease inhibition. Importantly, levels of apoA-IV were significantly reduced in ACS patients, whereas levels of serum amyloid A (SAA) and complement C3 (C3) were significantly increased (spectral counting; t-test p≤0.05), as confirmed by immunoblot or ELISA. Despite differences in protein composition, ABCA1, ABCG1, and SR-BI mediated cholesterol efflux assays did not indicate that HDL from ACS patients is functionally deficient as compared to controls, when corrected for apoA-I mass. Our results support that the HDL proteome differs between control, CAD and ACS patients. Increased abundance of SAA, C3, and other inflammatory proteins in HDL from ACS patients suggests that HDL reflects a shift to an inflammatory profile which, in turn, might alter the protective effects of HDL on the atherosclerotic plaque. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).
炎症是急性冠状动脉综合征（ACS）的主要潜在因素。在ACS中所见的炎症条件下，高密度脂蛋白（HDL）颗粒可能会发生重塑，导致功能缺陷。采用鸟枪法蛋白质组学监测年龄匹配的男性对照、稳定型冠心病和ACS患者（每组n = 10）之间HDL蛋白质组的变化。通过超速离心分离HDL，经一维凝胶分离后进行液相色谱-串联质谱分析。我们鉴定出67种与HDL相关的蛋白质，其中20种证实了最近鉴定出的蛋白质，包括玻连蛋白和补体C4B，还有5种是新发现的。通过基因本体分析，我们发现HDL蛋白质组由参与胆固醇稳态的蛋白质组成（约50%），参与脂质结合、抗氧化、急性期反应、免疫反应以及内肽酶/蛋白酶抑制的蛋白质也有显著贡献。重要的是，ACS患者载脂蛋白A-IV水平显著降低，而血清淀粉样蛋白A（SAA）和补体C3（C3）水平显著升高（光谱计数；t检验p≤0.05），免疫印迹或酶联免疫吸附测定证实了这一点。尽管蛋白质组成存在差异，但在校正载脂蛋白A-I质量后，ABCA1、ABCG1和SR-BI介导的胆固醇流出试验并未表明ACS患者的HDL与对照组相比功能存在缺陷。我们的结果支持对照、冠心病和ACS患者之间HDL蛋白质组存在差异。ACS患者HDL中SAA、C3和其他炎症蛋白丰度增加表明HDL反映了向炎症状态的转变，这反过来可能会改变HDL对动脉粥样硬化斑块的保护作用。本文是名为《高密度脂蛋白形成与代谢进展：向约翰·F·奥勒姆致敬（1945 - 2010）》特刊的一部分。
