Gebhard Catherine, Rhéaume Eric, Berry Colin, Brand Geneviève, Kernaleguen Anne-Elen, Théberge-Julien Gabriel, Alam Mohammad Afaque, Lee Candace Y W, Boileau Laurianne, Chabot-Blanchet Malorie, Guertin Marie-Claude, Lavoie Marc-André, Grégoire Jean, Ibrahim Réda, L'Allier Philippe, Tardif Jean-Claude
Montreal Heart Institute, Montreal, Quebec, Canada.
Université de Montréal, Montreal, Quebec, Canada.
PLoS One. 2017 Jan 6;12(1):e0168448. doi: 10.1371/journal.pone.0168448. eCollection 2017.
High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS.
The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6-7 weeks (i.e. 2-3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1.
The relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms.
高密度脂蛋白（HDL）对内皮祖细胞（EPC）具有有益影响。急性冠状动脉综合征（ACS）患者的循环祖细胞水平和功能受损。本研究调查了重组HDL（rHDL）对ACS患者循环祖细胞的短期影响。
研究人群包括33例近期ACS患者：20例来自ERASE试验（随机接受4次每周静脉输注40mg/kg CSL-111或安慰剂），另外13例患者按照相同入选标准招募作为对照。在基线时以及6-7周（即ERASE试验中第四次输注CSL-111后2-3周）从16例接受rHDL（CSL-111）治疗的患者和17例对照中采集血液。通过流式细胞术分析CD34+和CD34+/激酶插入结构域受体（KDR+）祖细胞计数。我们发现，随访时CSL-111治疗的受试者中CD34+细胞计数保持不变（变化1.6%），而对照组中CD34+细胞数量减少（-32.9%）（两组间p=0.017）。参与祖细胞募集的趋化因子循环基质细胞衍生因子-1（SDF-1）水平在对照组中显著升高（变化21.5%），而在CSL-111治疗的患者中保持不变（两组间p=0.031）。从健康志愿者分离的早期EPC体外暴露于CSL-111可显著增加CD34+细胞，减少早期EPC凋亡，并增强其向SDF-1的迁移能力。
ACS患者输注rHDL后观察到的循环CD34+细胞相对增加以及低SDF-1水平表明rHDL在心血管修复机制中发挥作用。
