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

• Published in: PloS one Vol. 12; no. 1; p. e0168448
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2017; Public Library of Science (PLoS)
• Subjects: Acute Coronary Syndrome - drug therapy; Acute coronary syndromes; Antigens, CD34; Apoptosis; Atherosclerosis; Biology and Life Sciences; Bone marrow; Cardiovascular disease; CD34 antigen; Cell Adhesion - drug effects; Cell Movement - drug effects; Cells (biology); Cholesterol; Cholesterol, HDL - therapeutic use; Cytometry; Diabetes; Endothelial Progenitor Cells - drug effects; Female; Flow cytometry; Heart attacks; High density lipoprotein; Humans; Intravenous administration; Lipoproteins; Low density lipoprotein; Male; Medicine and Health Sciences; Middle Aged; Patients; Phosphatidylcholines - therapeutic use; Population studies; Progenitor cells; Research and Analysis Methods; SDF-1 protein; Stem cells; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168448

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.