Beneficial effects of reconstituted high-density lipoprotein (rHDL) on circulating CD34+ cells in patients after an acute coronary syndrome

Gebhard, C. et al. (2017) Beneficial effects of reconstituted high-density lipoprotein (rHDL) on circulating CD34+ cells in patients after an acute coronary syndrome. PLoS ONE, 12(1), e0168448. (doi:10.1371/journal.pone.0168448) (PMID:28060837) (PMCID:PMC5218493)

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Abstract

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.

Item Type:Articles
Additional Information:: Dr. Lee was supported by the MerckFrosst Cardio-Metabolic Fellowship at the Montreal Heart Institute. Dr. Tardif holds the Canada Research Chair in translational and personalised medicine and the endowed research chair in atherosclerosis at the Universite´ de Montre´al. Dr. Gebhard was supported by the Swiss National Science Foundation (SNSF), the Swiss Foundation for Grants in Biology and Medicine (SFGBM) and the Novartis Jubilee Foundation, Switzerland. CSL111 was the generous gift of CSL Limited (Parkville, Australia). Dr. Berry was supported by an International Fellowship from the British Heart Foundation
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Berry, Professor Colin
Authors: Gebhard, C., Rhéaume, E., Berry, C., Brand, G., Kernaleguen, A.-E., Théberge-Julien, G., Alam, M. A., Lee, C. Y.W., Boileau, L., Chabot-Blanchet, M., Guertin, M.-C., Lavoie, M.-A., Grégoire, J., Ibrahim, R., L'Allier, P., and Tardif, J.-C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2017 Gebhard et al.
First Published:First published in PLoS ONE 12(1): e0168448
Publisher Policy:Reproduced under a Creative Commons License

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