Krzesińska Aleksandra, Marlęga-Linert Joanna, Chyła-Danił Gabriela, Marcinkowska Marta, Rogowska Paulina, Stumska Katarzyna, Fijałkowski Marcin, Gruchała Marcin, Jankowski Maciej, Mickiewicz Agnieszka, Kuchta Agnieszka
Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
1st Department of Cardiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
Int J Mol Sci. 2024 Dec 19;25(24):13597. doi: 10.3390/ijms252413597.
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.
脂蛋白的氧化修饰在动脉粥样硬化性心血管疾病(ASCVD)的发病过程中起着关键作用。如今,治疗高脂蛋白血症(a)患者的一种有效策略是脂蛋白分离术(LA),它对降低ASCVD风险具有多效性作用。LDL组分的氧化易感性在ASCVD中的意义已得到广泛研究。LA是否会改变脂蛋白(a)对氧化修饰的易感性仍是一个未解决的问题。在本研究中,我们通过超速离心法在三个时间点分离了接受分离术的高脂蛋白血症(a)患者(LA组)以及符合LA条件但不同意进行该操作的患者(非LA组)的脂蛋白组分。我们对Lp(a)和LDL组分进行了铜介导的氧化,并测定了自分泌运动因子活性。分离术后,我们观察到Lp(a)和LDL组分的氧化易感性降低,表现为氧化滞后时间延长、氧化曲线斜率降低以及共轭二烯最终浓度降低。LA前后这些参数之间未发现显著差异。此外,接受和未接受LA的患者中,自分泌运动因子活性与Lp(a)组分中所有氧化易感性特征参数之间均存在显著相关性。我们的结果表明,分离术的多效性作用可能与Lp(a)和LDL颗粒氧化易感性降低有关,这可能会影响接受分离术患者ASCVD风险的降低。LA后7天的反弹效应结果将有助于更好地确定分离术频率指南。