Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Sci Rep. 2018 Nov 23;8(1):17301. doi: 10.1038/s41598-018-35034-x.
The prothrombotic fibrin clot phenotype has been reported in patients with thrombotic antiphospholipid syndrome (APS) and venous thromboembolism (VTE). Protein composition of plasma fibrin clots in APS has not been studied. We evaluated 23 patients with thrombotic APS, 19 with VTE alone, and 20 well-matched controls. A proteomic analysis of fibrin clots generated from citrated plasma was based on liquid chromatography-mass spectrometry. Plasma levels of thrombospondin-1 (TSP1), apolipoprotein(a), A-I, and B-100, complement components (C)3a, C5b-C9, histidine-rich glycoprotein (HRG), and prothrombin were evaluated using immunoenzymatic tests. In plasma fibrin clots of APS patients, compared with VTE subjects and controls, we identified decreased amounts of (pro)thrombin, antithrombin-III, apolipoprotein A-I, and HRG with no differences in plasma levels of antithrombin, prothrombin, along with lower plasma HRG and apolipoprotein A-I. In APS patients, plasma HRG positively correlated with amounts of clot-bound HRG, while apolipoprotein A-I was inversely associated with clot-bound levels of this protein. The most predominant proteins within the clots of APS patients were bone marrow proteoglycan, C5-C9, immunoglobulins, apolipoprotein B-100, platelet-derived proteins, and TSP1. Our study is the first to demonstrate differences in the protein composition of fibrin clots generated from plasma of thrombotic APS patients versus those with VTE alone.
已有研究报道，在血栓性抗磷脂综合征（APS）和静脉血栓栓塞症（VTE）患者中存在促血栓形成的纤维蛋白凝块表型。APS 患者血浆纤维蛋白凝块的蛋白组成尚未得到研究。我们评估了 23 例血栓性 APS 患者、19 例单纯 VTE 患者和 20 例匹配良好的对照者。基于液相色谱-质谱法对来源于枸橼酸盐血浆的纤维蛋白凝块进行了蛋白质组学分析。采用免疫酶检测法评估了血栓调节蛋白-1（TSP1）、载脂蛋白（a）、A-I 和 B-100、补体成分（C）3a、C5b-C9、组氨酸丰富糖蛋白（HRG）和凝血酶原的血浆水平。与 VTE 患者和对照组相比，我们发现 APS 患者血浆纤维蛋白凝块中（pro）凝血酶、抗凝血酶-III、载脂蛋白 A-I 的含量减少，而抗凝血酶、凝血酶原的血浆水平无差异，同时 HRG 和载脂蛋白 A-I 的血浆水平也较低。在 APS 患者中，血浆 HRG 与纤维蛋白凝块中 HRG 的含量呈正相关，而载脂蛋白 A-I 与纤维蛋白凝块中该蛋白的含量呈负相关。APS 患者凝块中含量最丰富的蛋白为骨髓蛋白聚糖、C5-C9、免疫球蛋白、载脂蛋白 B-100、血小板衍生蛋白和 TSP1。本研究首次证明了血栓性 APS 患者与单纯 VTE 患者血浆生成的纤维蛋白凝块的蛋白组成存在差异。
