Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
4th Department of Internal Medicine-Hematology, University Hospital Hradec Králové, 50005 Hradec Králové, Czech Republic.
Genes (Basel). 2023 Aug 1;14(8):1571. doi: 10.3390/genes14081571.
Lipoprotein apheresis (LA) is a therapeutic option for patients with severe hypercholesterolemia who have persistently elevated LDL-C levels despite attempts at drug therapy. MicroRNAs (miRNAs), important posttranscriptional gene regulators, are involved in the pathogenesis of atherosclerosis. Our study aimed to monitor the dynamics of twenty preselected circulating miRNAs in patients under long-term apheresis treatment. Plasma samples from 12 FH patients (men = 50%, age = 55.3 ± 12.2 years; mean LA overall treatment time = 13.1 ± 7.8 years) were collected before each apheresis therapy every sixth month over the course of four years of treatment. Eight complete follow-up (FU) samples were measured in each patient. Dynamic changes in the relative quantity of 6 miRNAs (miR-92a, miR-21, miR-126, miR-122, miR-26a, and miR-185; all < 0.04) during FU were identified. Overall apheresis treatment time influenced circulating miR-146a levels ( < 0.04). In LDLR mutation homozygotes (N = 5), compared to heterozygotes (N = 7), we found higher plasma levels of miR-181, miR-126, miR-155, and miR-92a (all < 0.03). Treatment with PCSK9 inhibitors (N = 6) affected the plasma levels of 7 miRNAs (miR-126, miR-122, miR-26a, miR-155, miR-125a, miR-92a, and miR-27a; all < 0.04). Long-term monitoring has shown that LA in patients with severe familial hypercholesterolemia influences plasma circulating miRNAs involved in endothelial dysfunction, cholesterol homeostasis, inflammation, and plaque development. The longer the treatment using LA, the better the miRNA milieu depicting the potential cardiovascular risk.
脂蛋白吸附术（LA）是一种治疗选择，适用于患有严重高胆固醇血症的患者，这些患者尽管尝试了药物治疗，但 LDL-C 水平仍持续升高。微小 RNA（miRNA）是重要的转录后基因调控因子，参与动脉粥样硬化的发病机制。我们的研究旨在监测长期接受吸附治疗的患者中 20 种预选循环 miRNA 的动态变化。从 12 名 FH 患者（男性占 50%，年龄 55.3 ± 12.2 岁；平均 LA 总治疗时间 13.1 ± 7.8 年）中采集血浆样本，在治疗的四年中，每六个月在每次吸附治疗前采集一次。每个患者测量了 8 个完整的随访（FU）样本。在 FU 期间，确定了 6 种 miRNA（miR-92a、miR-21、miR-126、miR-122、miR-26a 和 miR-185；均<0.04）相对数量的动态变化。总体 LA 治疗时间影响循环 miR-146a 水平（<0.04）。在 LDLR 突变纯合子（N=5）中，与杂合子（N=7）相比，我们发现 miR-181、miR-126、miR-155 和 miR-92a 的血浆水平更高（均<0.03）。使用 PCSK9 抑制剂治疗（N=6）影响了 7 种 miRNA（miR-126、miR-122、miR-26a、miR-155、miR-125a、miR-92a 和 miR-27a；均<0.04）的血浆水平。长期监测表明，在严重家族性高胆固醇血症患者中，LA 影响参与内皮功能障碍、胆固醇稳态、炎症和斑块形成的血浆循环 miRNA。LA 治疗时间越长，描绘潜在心血管风险的 miRNA 环境就越好。
