Gurevitz Chen, Zadok Osnat Itzhaki Ben, Leshem-Lev Dorit, Hodeda Lital, Rotholz Aviad, Kornowski Ran, Eisen Alon
Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel.
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Am J Prev Cardiol. 2024 Nov 16;20:100896. doi: 10.1016/j.ajpc.2024.100896. eCollection 2024 Dec.
The role of circulating endothelial progenitor cells (cEPCs) in vascular repair and their association to cardiovascular protection is well established.
We examined the effect of proprotein convertase subtilisin kexin type 9 monoclonal antibodies (PCSK9 mAb) on cEPCs in adults with hypercholesterolemia and cardiovascular disease, aiming to establish a pleotropic class effect.
Non-interventional prospective study in patients with cardiovascular disease treated with either evolocumab or alirocumab. Patients were sampled for cEPCs at baseline, 1- and 3-months following initiation of PCSK9 mAb. cEPCs were assessed using flow cytometry by expression of CD34/CD133 and vascular endothelial growth factor receptor (VEGFR)-2, and functionally by formation of colony forming units (CFUs) and by Mitochondrial Tetrazolium (MTT) assay, indicative of cEPCs viability.
51 patients (median age 67 (IQR 63,74) years;63 % male, median low-density lipoprotein-cholesterol (LDL-C) 125 (102,165) mg/dL) were initiated on PCSK9 mAb therapy (evolocumab = 22, alirocumab = 29) for secondary prevention. Following 3-month treatment with PCSK9 mAb, there was an increase in CD34VEGFR-2 and CD133VEGFR-2 levels (0.50 % [IQR 0.30,1.04] to 1.36 % [0.89, 1.73], < 0.001 and 0.57 % [0.25,0.88] to 1.18 % [0.74,1.66], < 0.001, respectively). Functionally, increase in EPCs-CFUs was evident (0.5 [0.0,1.0] to 2.0 [1.5,2.5], < 0.001) with concomitant increase in MTT (0.11 [0.09,0.15] to 0.17 [0.12,0.21], < 0.001). Stratifying by PCSK9 mAb, both agents were associated with an increase in cEPCs level and function.
In hypercholesterolemic patients with cardiovascular disease treated with PCSK9 mAb, there is an increase in cEPCs levels and function from baseline levels. These findings, which persist in both evolocumab and alirocumab, might suggest a novel pleiotropic class effect.
循环内皮祖细胞（cEPCs）在血管修复中的作用及其与心血管保护的关联已得到充分证实。
我们研究了前蛋白转化酶枯草溶菌素9型单克隆抗体（PCSK9 mAb）对患有高胆固醇血症和心血管疾病的成年人cEPCs的影响，旨在确立一种多效性的类别效应。
对接受依洛尤单抗或阿利西尤单抗治疗的心血管疾病患者进行非干预性前瞻性研究。在开始使用PCSK9 mAb治疗的基线、1个月和3个月时采集患者的cEPCs样本。通过流式细胞术检测cEPCs中CD34/CD133和血管内皮生长因子受体（VEGFR）-2的表达，并通过集落形成单位（CFUs）的形成以及线粒体四氮唑（MTT）试验从功能上评估cEPCs，MTT试验可指示cEPCs的活力。
51例患者（中位年龄67（四分位间距63,74）岁；63%为男性，中位低密度脂蛋白胆固醇（LDL-C）为125（102,165）mg/dL）开始接受PCSK9 mAb治疗（依洛尤单抗=22例，阿利西尤单抗=29例）用于二级预防。接受PCSK9 mAb治疗3个月后，CD34VEGFR-2和CD133VEGFR-2水平升高（分别从0.50%[四分位间距0.30,1.04]升至1.36%[0.89,1.73]，P<0.001；从0.57%[0.25,0.88]升至1.18%[0.74,1.66]，P<0.001）。在功能上，EPCs-CFUs明显增加（从0.5[0.0,1.0]升至2.0[1.5,2.5]，P<0.001），同时MTT增加（从0.11[0.09,0.15]升至0.17[0.12,0.21]，P<0.001）。按PCSK9 mAb分层，两种药物均与cEPCs水平和功能的增加相关。
在接受PCSK9 mAb治疗的高胆固醇血症心血管疾病患者中，cEPCs水平和功能较基线水平有所增加。这些在依洛尤单抗和阿利西尤单抗治疗中均持续存在的发现，可能提示一种新的多效性类别效应。
