Clinical Trials Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Nov 26, 2020; 12(11): 526-539
Published online Nov 26, 2020. doi: 10.4330/wjc.v12.i11.526
Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity
Christos Kourek, Eleftherios Karatzanos, Katherina Psarra, Georgios Georgiopoulos, Dimitrios Delis, Vasiliki Linardatou, Gerasimos Gavrielatos, Costas Papadopoulos, Serafim Nanas, Stavros Dimopoulos
Christos Kourek, Eleftherios Karatzanos, Dimitrios Delis, Vasiliki Linardatou, Serafim Nanas, Department of Clinical Ergospirometry, Exercise & Rehabilitation Laboratory, Evaggelismos Hospital, Athens 10676, Greece
Katherina Psarra, Immunology and Histocompatibility Department, Evaggelismos Hospital, Athens 10676, Greece
Georgios Georgiopoulos, Department of Clinical Therapeutics, Alexandra Hospital, Athens 11528, Greece
Gerasimos Gavrielatos, Department of Cardiology, Tzaneio General Hospital of Piraeus, Piraeus 18536, Greece
Costas Papadopoulos, 2nd Cardiology Department, Korgialenio-Benakio Red Cross Hospital, Athens 11526, Greece
Stavros Dimopoulos, Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece
Author contributions: Karatzanos E, Nanas S and Dimopoulos S contributed to the conception and design of the study; Kourek C, Delis D, Linardatou V, Gavrielatos G and Papadopoulos C contributed to the acquisition and interpretation of data; Kourek C, Karatzanos E, Georgiopoulos G and Psarra K performed the analysis; Kourek C drafted the manuscript; All authors contributed equally to the critical revision, editing and approval of the final version of the manuscript.
Supported by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project “Strengthening Human Resources Research Potential via Doctorate Research”(MIS-5000432), implemented by the State Scholarships Foundation (ΙΚΥ); and the special account for research grants of the National and Kapodistrian University of Athens, Athens, Greece.
Institutional review board statement: The study was reviewed and approved by the Administration Board and the Ethics Committee of “Evaggelismos General Hospital” in Athens, Greece.
Clinical trial registration statement: This study is registered at Evaggelismos General Hospital of Athens trial registry. The registration identification number is 117/3-7-2017.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors state they have no real or potential conflicts-of-interest to declare.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Stavros Dimopoulos, MD, PhD, Doctor, Postdoc, Research Scientist, Senior Researcher, Staff Physician, Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, No. 356 L. Syggrou, Athens 17674, Greece. stdimop@gmail.com
Received: June 24, 2020
Peer-review started: June 24, 2020
First decision: July 25, 2020
Revised: July 28, 2020
Accepted: October 5, 2020
Article in press: October 5, 2020
Published online: November 26, 2020
Abstract
BACKGROUND

Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation.

AIM

To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity.

METHODS

Forty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO2, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34+/CD45-/CD133+, CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2 (VEGFR2)] and two subgroups of circulating endothelial cells (CD34+/CD45-/CD133- and CD34+/CD45-/CD133-/VEGFR2). Patients were divided in two groups of severity according to the median value of peak VO2 (18.0 mL/kg/min), predicted peak VO2 (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/106 enucleated cells.

RESULTS

Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133+/VEGFR2 [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/106 enucleated cells, P < 0.001] and CD34+/CD45-/CD133-/VEGFR2 [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/106 enucleated cells, P < 0.001], while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133+/VEGFR2 [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/106 enucleated cells, P < 0.001], CD34+/CD133+/VEGFR2 [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/106 enucleated cells, P < 0.01], CD34+/CD45-/CD133- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/106 enucleated cells, P < 0.001] and CD34+/CD45-/CD133-/VEGFR2 [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/106 enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05).

CONCLUSION

Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.

Keywords: Chronic heart failure, Endothelial progenitor cells, Circulating endothelial cells, Maximal exercise, Cardiopulmonary exercise testing, Severity

Core Tip: Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Exercise has been proven to increase the mobilization of endothelial progenitor cells (EPCs), which are involved in vascular endothelial restoration and neo-vascularization, in healthy people and patients with co-morbidities. However, the effect of exercise on EPCs in patients with CHF of different severity remains unknown. In the present study, we compared the mobilization of EPCs in CHF patients of different severity, according to functional markers, after a symptom-limited cardiopulmonary exercise testing. No differences were found between severity groups, indicating thus the beneficial effect of exercise in these patients.