Apolipoproteins and lipoprotein(a) as factors modulating fibrin clot properties in patients with severe aortic stenosis

• Published in: Atherosclerosis 2022-03, Vol.344, p.49-56
• Main Authors: Siudut, Jakub, Natorska, Joanna, Wypasek, Ewa, Wiewiórka, Łukasz, Ostrowska-Kaim, Elżbieta, Wiśniowska-Śmiałek, Sylwia, Plens, Krzysztof, Musialek, Piotr, Legutko, Jacek, Undas, Anetta
• Format: Article
• Language: English
• Subjects: Aortic stenosis; Aortic Valve Stenosis; Apolipoproteins; Apolipoproteins B; Fibrin - analysis; Fibrin Clot Lysis Time; Fibrinolysis; Humans; lipoprotein(a); Lipoproteins; Oxidized low-density lipoproteins; Proteomics
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2022.01.011

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 (MaxAbsCLT2018 and MaxAbsLys50), 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 MaxAbsCLT2018 and MaxAbsLys50, 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 MaxAbsCLT2018, -53.2% lower MaxAbsLys50, 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. [Display omitted] •Apolipoproteins contribute to prothrombotic fibrin clot phenotype in severe aortic stenosis (AS).•Apolipoproteins could predict hypofibrinolysis better than serum lipids.•Statins have beneficial effects on fibrin clot structure and function in severe AS.