Beneficial Effects of Reconstituted High-Density Lipoprotein (rHDL) on Circulating CD34(+) Cells in Patients after an Acute Coronary Syndrome

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.