Sradnick Jan, Tselmin Sergey, Wagner Andrea, Julius Ulrich, Todorov Vladimir, Hugo Christian, Hohenstein Bernd
Division of Nephrology, Department of Internal Medicine III, University Hospital and Faculty of Medicine Carl Gustav Carus at the Technische Universität, Dresden, Germany.
Extracorporeal Treatment and Apheresis Center, Department of Internal Medicine III, University Hospital and Faculty of Medicine Carl Gustav Carus at the Technische Universität, Dresden, Germany.
Atheroscler Suppl. 2017 Nov;30:232-237. doi: 10.1016/j.atherosclerosissup.2017.05.045. Epub 2017 Jun 2.
Severe forms of mono- and polygenetic hypercholesterolemia as well as elevated Lipoprotein (a) (LP(a)) with progressing cardiovascular (CV) disease are indication for lipoprotein apheresis (LA) in Germany. Many studies investigated pleiotropic effects of LA that might contribute to beneficial effects in advanced atherosclerosis. The present study aimed at investigating the potential role of Proangiogenic Cells (PAC) in patients with new onset or chronic LA using the heparin induced extracorporeal LDL-precipitation (H.E.L.P.) apheresis system.
Patients (n = 10) new to LA and HELP treatment were investigated immediately before, shortly after, 24 h later and 4 weeks following LA. Peripheral blood was used to count PAC in circulation via flow cytometry. In a second step, blood cells from patients were cultured in endothelial selective medium and further evaluated for adhesion in fibronectin coated chamber slides and migratory capacity (stromal cell-derived factor-1 (SDF-1) induced migration).
Cells expressing typical EPC markers were rarely detected in blood samples. No differences occurred over time in CD34; CD34 CD133 CD45; CD34/KDR and CXCR4/CD14 positive PAC. We found no differences in cell adhesion at the different time points, while significantly more cells migrated into the SDF-1 medium following four weeks of continuing apheresis therapy.
Using well established systems, this study was not able to demonstrate relevant acute effects of LA on PAC in patients new to LA. The increased migratory capacity of PAC might be an indicator of chronic beneficial pleiotropic effects in patients undergoing H.E.L.P. apheresis.
在德国，严重的单基因和多基因高胆固醇血症以及伴有进展性心血管疾病的脂蛋白(a) [LP(a)] 升高是脂蛋白分离术 (LA) 的适应症。许多研究调查了LA的多效性作用，这些作用可能有助于对晚期动脉粥样硬化产生有益影响。本研究旨在使用肝素诱导的体外低密度脂蛋白沉淀 (H.E.L.P.) 分离系统，调查新生或慢性LA患者中促血管生成细胞 (PAC) 的潜在作用。
对初次接受LA和HELP治疗的患者（n = 10）在LA治疗前、治疗后不久、24小时后以及治疗后4周进行调查。使用外周血通过流式细胞术计数循环中的PAC。第二步，将患者的血细胞在内皮细胞选择性培养基中培养，并进一步评估其在纤连蛋白包被的腔室载玻片上的黏附能力和迁移能力（基质细胞衍生因子-1 [SDF-1] 诱导的迁移）。
在血样中很少检测到表达典型内皮祖细胞标志物的细胞。CD34；CD34 CD133 CD45；CD34/KDR和CXCR4/CD14阳性PAC在不同时间没有差异。我们发现在不同时间点细胞黏附没有差异，而在持续进行四周的分离治疗后，迁移到SDF-1培养基中的细胞明显更多。
使用成熟的系统，本研究未能证明LA对初次接受LA治疗的患者的PAC有相关急性作用。PAC迁移能力的增加可能是接受H.E.L.P. 分离术治疗的患者慢性有益多效性作用的一个指标。
