Proteomic analysis of proteins eliminated by low-density lipoprotein apheresis

Abstract

Low-density lipoprotein apheresis (LDL-A) treatment has been shown to decrease serum LDL cholesterol levels and prevent cardiovascular events in homozygous patients with familial hypercholesterolemia. Recently, LDL-A treatment has been suggested to have beneficial effects beyond the removal of LDL particles. In this study, to clarify the preventive effects of LDL-A treatment on atherosclerosis, the waste fluid from the adsorption columns was analyzed. The waste fluid of LDL adsorption columns was analyzed by two-dimensional electrophoresis followed by mass spectrometry. Serum concentrations of the newly identified proteins before and after LDL-A treatment were measured by enzyme-linked immunosorbent assay. We identified 48 kinds of proteins in the waste fluid of LDL adsorption columns, including coagulation factors, thrombogenic factors, complement factors, inflammatory factors and adhesion molecules. In addition to the proteins that were reported to be removed by LDL-A treatment, we newly identified several proteins that have some significant roles in the development of atherosclerosis, including vitronectin and apolipoprotein C-III (Apo C-III). The serum levels of vitronectin and Apo C-III decreased by 82.4% and 54.8%, respectively, after a single LDL-A treatment. While Apo C-III was removed with very low-density lipoprotein (VLDL) and LDL, vitronectin was removed without association with lipoproteins. The removal of proteins observed in the waste fluid has a certain impact on their serum levels, and this may be related to the efficacy of LDL-A treatment. Proteomic analysis of the waste fluid of LDL adsorption columns may provide a rational means of assessing the effects of LDL-A treatment.

Keywords: Apolipoprotein C-III; Low-density lipoprotein apheresis; Proteomic analysis; Vitronectin.