Lipoprotein apheresis reduces oxidative susceptibility of both Lp(a) and LDL particles, a possible mechanism behind its cardiovascular benefit (Int J Mol Sci 2024)

Oxidative modifications of lipoproteins play a crucial role in the initiation of atherosclerotic cardiovascular diseases (ASCVDs). Nowadays, the one effective strategy for the treatment of patients with hyperlipoproteinemia(a) is lipoprotein apheresis (LA), which has a pleiotropic effect on reducing the risk of ASCVDs. The significance of oxidative susceptibility of the LDL fraction in ASCVDs has been extensively studied. Whether LA alters the susceptibility of lipoprotein(a) to oxidative modifications remains an unresolved issue. In this study, we isolated lipoprotein fractions by ultracentrifugation in patients with hyperlipoproteinemia(a) undergoing apheresis (LA group) at three time points and patients who were qualified for LA but did not consent to the procedure (non-LA group). We performed copper-mediated oxidation of Lp(a) and LDL fractions and determined autotaxin activity. After apheresis, we observed a lower susceptibility to oxidation of the Lp(a) and LDL fractions as expressed by the extended value of oxidation lag time, decreased slope of the oxidation curve, and decreased final concentration of conjugated dienes. No significant differences were found between these parameters before and 7 days after LA. Additionally, both patients undergoing and not undergoing LA had a significant correlation between autotaxin activity and all parameters characterizing susceptibility to oxidation in the Lp(a) fraction. Our results demonstrate that the pleiotropic effect of apheresis may be related to the reduced oxidative susceptibility of Lp(a) and LDL particles, which may influence the reduction in ASCVD risk in patients undergoing apheresis. The results of the rebound effect 7 days after LA will contribute to a better definition of apheresis frequency guidelines.