RD3-Pharmacognosy, Bioanalysis and Drug Discovery, Faculty of Pharmacy, Université Libre de Bruxelles, 1050 Brussels, Belgium.
Laboratoire Hospitalier Universitaire de Bruxelles (LHUB-ULB), Department of Clinical Chemistry, Université Libre de Bruxelles (ULB), 1000 Brussels, Belgium.
Molecules. 2021 Aug 30;26(17):5264. doi: 10.3390/molecules26175264.
Oxidative modifications of HDLs and LDLs by myeloperoxidase (MPO) are regularly mentioned in the context of atherosclerosis. The enzyme adsorbs on protein moieties and locally produces oxidizing agents to modify specific residues on apolipoproteins A-1 and B-100. Oxidation of lipoproteins by MPO (Mox) leads to dysfunctional Mox-HDLs associated with cholesterol-efflux deficiency, and Mox-LDLs that are no more recognized by the LDL receptor and become proinflammatory. Several modification sites on apoA-1 and B-100 that are specific to MPO activity are described in the literature, which seem relevant in patients with cardiovascular risk. The most appropriate analytical method to assess these modifications is based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). It enables the oxidized forms of apoA-1and apoB-100 to be quantified in serum, in parallel to a quantification of these apolipoproteins. Current standard methods to quantify apolipoproteins are based on immunoassays that are well standardized with good analytical performances despite the cost and the heterogeneity of the commercialized kits. Mass spectrometry can provide simultaneous measurements of quantity and quality of apolipoproteins, while being antibody-independent and directly detecting peptides carrying modifications for Mox-HDLs and Mox-LDLs. Therefore, mass spectrometry is a potential and reliable alternative for apolipoprotein quantitation.
髓过氧化物酶（MPO）对 HDL 和 LDL 的氧化修饰经常在动脉粥样硬化的背景下被提及。该酶吸附在蛋白质部分，局部产生氧化剂，修饰载脂蛋白 A-1 和 B-100 上的特定残基。MPO（Mox）对脂蛋白的氧化作用导致功能失调的 Mox-HDL，与胆固醇外排缺陷相关，以及不再被 LDL 受体识别的 Mox-LDL，成为促炎的。文献中描述了一些特定于 MPO 活性的载脂蛋白 A-1 和 B-100 的修饰位点，这些位点在心血管风险患者中似乎具有相关性。评估这些修饰的最合适的分析方法基于液相色谱-串联质谱（LC-MS/MS）。它能够定量血清中载脂蛋白 A-1 和载脂蛋白 B-100 的氧化形式，同时定量这些载脂蛋白。目前用于定量载脂蛋白的标准方法基于免疫测定法，尽管试剂盒的成本和异质性，但这些免疫测定法具有良好的标准化和良好的分析性能。质谱法可以提供载脂蛋白数量和质量的同时测量，同时不依赖抗体，直接检测携带 Mox-HDL 和 Mox-LDL 修饰的肽。因此，质谱法是载脂蛋白定量的一种有潜力和可靠的替代方法。
