a Department of Chemistry, Atherothrombosis Research Center/Laboratory of Biochemistry , University of Ioannina , Ioannina , Greece.
b Department of Cardiology , School of Medicine, University of Ioannina , Ioannina , Greece.
Platelets. 2019;30(3):314-321. doi: 10.1080/09537104.2018.1430355. Epub 2018 Feb 16.
CD34 cells expressing KDR (CD34/KDR) represent a small proportion of circulating progenitor cells that have the capacity to interact with platelets and to differentiate into mature endothelial cells, thus contributing to vascular homeostasis and regeneration as well as to re-endothelialization. We investigated the levels of CD34 and CD34/KDR progenitor cells as well as their interaction with platelets in acute coronary syndrome (ACS) patients before the initiation (baseline) of their treatment with a P2Y receptor antagonist, and at 5-days post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty healthy subjects (controls) participated in the study. On admission, all patients received 325 mg aspirin, followed by 100 mg/day and then were loaded either with 600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg × 2/day (n = 31), respectively. The levels of circulating CD34 and CD34/KDR progenitor cells, as well as their interaction with platelets, were determined by flow cytometry, before and after activation with ADP, in vitro. The circulating levels of CD34 and CD34/KDR cells in both patient groups at baseline were lower compared with controls while they were significantly increased at 5-days of follow-up in both groups, this increase being more pronounced in the ticagrelor group. The platelet/CD34 (CD61/CD34) conjugates were higher at baseline and reduced at follow-up while the platelet/KDR (CD61/KDR) conjugates were lower at baseline and increased at follow-up, both changes being more pronounced in the ticagrelor group. ADP activation of control samples significantly increased the KDR expression by CD34 cells and the CD61/KDR conjugates, these parameters being unaffected in patients at baseline but increased at follow-up. Short-term dual antiplatelet therapy in ACS patients restores the low platelet/KDR conjugates and CD34 cell levels and improves the low membrane expression levels of KDR in these cells, an effect being more pronounced in ticagrelor-treated patients. This may represent a pleiotropic effect of antiplatelet therapy towards vascular endothelial regeneration.
CD34 细胞表达 KDR（CD34/KDR）代表循环祖细胞中的一小部分，它们具有与血小板相互作用并分化为成熟内皮细胞的能力，从而有助于血管内稳态和再生以及再内皮化。我们研究了急性冠状动脉综合征（ACS）患者在开始（基线）接受 P2Y 受体拮抗剂治疗之前以及治疗后 5 天（随访）时 CD34 和 CD34/KDR 祖细胞的水平及其与血小板的相互作用。67 例连续 ACS 患者和 30 例健康受试者（对照组）参加了这项研究。入院时，所有患者均接受 325mg 阿司匹林治疗，随后每日 100mg 治疗，然后分别给予 600mg 氯吡格雷或 180mg 替格瑞洛负荷剂量，随后每日 75mg（n=36）或每日 90mg×2 次（n=31）。通过流式细胞术，在体外用 ADP 激活之前和之后，分别测定循环 CD34 和 CD34/KDR 祖细胞的水平及其与血小板的相互作用。与对照组相比，两组患者基线时的循环 CD34 和 CD34/KDR 细胞水平均较低，而两组患者在随访 5 天时均显著升高，其中替格瑞洛组升高更为明显。血小板/CD34（CD61/CD34）结合物在基线时较高，随访时降低，而血小板/KDR（CD61/KDR）结合物在基线时较低，随访时升高，这些变化在替格瑞洛组更为明显。ADP 激活对照样本可显著增加 CD34 细胞的 KDR 表达和 CD61/KDR 结合物，这些参数在基线时对患者无影响，但在随访时增加。ACS 患者短期双联抗血小板治疗可恢复低血小板/KDR 结合物和 CD34 细胞水平，并改善这些细胞中 KDR 膜表达水平较低的情况，替格瑞洛治疗患者的效果更为明显。这可能代表抗血小板治疗对血管内皮再生的多效性作用。
