Institute of Cardiology, Jagiellonian University Medical College, 31-202, Krakow, Poland; Krakow Center for Medical Research and Technologies, John Paul II Hospital, 31-202, Krakow, Poland.
Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705, Krakow, Poland.
Atherosclerosis. 2022 Mar;344:49-56. doi: 10.1016/j.atherosclerosis.2022.01.011. Epub 2022 Jan 25.
Large amounts of clot-bound lipoproteins were reported in proteomic analysis of plasma clot but their impact on fibrin clot properties is unknown. We investigated a contribution of lipid profile and apolipoproteins (apo) to the prothrombotic plasma fibrin clot phenotype in patients with aortic stenosis (AS).
In 138 patients with isolated severe AS, we determined serum apoA-I, A-II, B, C-II, C-III, E, oxidized low-density lipoprotein (OxLDL) and lipoprotein(a) concentrations. Plasma fibrin clot permeability (Ks), maximal absorbance (MaxAbs and MaxAbs), and fibrinolytic capacity were studied using 3 plasma-based lysis assays (CLT2018, CLT, and Lys50), and compared with well-matched patients without AS (control group).
After adjustment for confounding factors, including statin use, only low-density lipoprotein cholesterol (LDL-C) and apoB levels were inversely associated with Ks. Triglycerides, apoC-II, and C-III were associated with MaxAbs and MaxAbs, explaining 56-64% of their variability. CLT2018 and CLT showed associations with total cholesterol, LDL-C, triglycerides, and OxLDL as well as with apoB, C-II, C-III, and E. ApoA-I, C-II, and C-III but not serum lipids were associated with Lys50. Only CLT2018 was associated with lipoprotein(a). ApoC-III, B, A-I, and E along with estimated glomerular filtration rate and OxLDL predicted hypofibrinolysis in multiple regression analysis. AS patients had higher lipoprotein(a) (+34.9%) and apoA-I (+25.9%) levels and less compact fibrin clots (-13.3% lower MaxAbs, -53.2% lower MaxAbs, and +28.3% higher Ks) displaying higher susceptibility to lysis (-17.9% lower Lys50) in comparison with control group.
Apolipoproteins and OxLDL contribute to prothrombotic fibrin clot phenotype in severe AS. Moreover, apolipoproteins better than serum lipids predicted hypofibrinolysis, which provides additional argument for a role of elevated lipoproteins in the prothrombotic state.
大量的纤维蛋白凝块结合脂蛋白在血浆凝块的蛋白质组学分析中被报道，但它们对纤维蛋白凝块特性的影响尚不清楚。我们研究了脂质谱和载脂蛋白（apo）对主动脉瓣狭窄（AS）患者血栓前血浆纤维蛋白凝块表型的贡献。
在 138 例孤立性严重 AS 患者中，我们测定了血清 apoA-I、A-II、B、C-II、C-III、E、氧化低密度脂蛋白（OxLDL）和脂蛋白（a）浓度。使用 3 种基于血浆的溶解测定法（CLT2018、CLT 和 Lys50）研究了血浆纤维蛋白凝块通透性（Ks）、最大吸光度（MaxAbs 和 MaxAbs）和纤维蛋白溶解能力，并与匹配良好的无 AS 患者（对照组）进行了比较。
调整混杂因素（包括他汀类药物的使用）后，只有低密度脂蛋白胆固醇（LDL-C）和 apoB 水平与 Ks 呈负相关。甘油三酯、apoC-II 和 C-III 与 MaxAbs 和 MaxAbs 相关，解释了其变异性的 56-64%。CLT2018 和 CLT 与总胆固醇、LDL-C、甘油三酯和 OxLDL 以及 apoB、C-II、C-III 和 E 相关。apoA-I、C-II 和 C-III 但不是血清脂质与 Lys50 相关。只有 CLT2018 与脂蛋白（a）相关。载脂蛋白 C-III、B、A-I 和 E 以及估计的肾小球滤过率和 OxLDL 在多元回归分析中预测了纤溶活性降低。与对照组相比，AS 患者的脂蛋白（a）（+34.9%）和 apoA-I（+25.9%）水平更高，纤维蛋白凝块更不紧密（MaxAbs 降低 13.3%，MaxAbs 降低 53.2%，Ks 增加 28.3%），对溶解的敏感性更高（Lys50 降低 17.9%）。
载脂蛋白和 OxLDL 有助于严重 AS 中的血栓前纤维蛋白凝块表型。此外，载脂蛋白比血清脂质更好地预测纤溶活性降低，这为升高的脂蛋白在血栓前状态中的作用提供了额外的证据。
