Elsevier

Journal of Cardiac Failure

Volume 13, Issue 9, November 2007, Pages 701-708
Journal of Cardiac Failure

Clinical Trial
Effects of Exercise Training on Endothelial Progenitor Cells in Patients With Chronic Heart Failure

https://doi.org/10.1016/j.cardfail.2007.06.722Get rights and content

Abstract

Background

The enhancement of circulating endothelial progenitor cells (EPCs) obtained by exercise training can be beneficial to patients with cardiac disease. Changes in the levels and differentiation of CD34pos/KDRpos EPCs, as well as the plasma concentration of vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1 EPC-mobilizing cytokines, were evaluated in patients with chronic heart failure after 8 weeks of supervised aerobic training (SAT) and 8 weeks of subsequent discontinued SAT (DSAT).

Methods and Results

The levels of circulating EPC and EPC differentiation potential of 22 patients who underwent SAT were studied by fluorescence-activated cell sorter analysis and colony forming-unit assay, respectively. The plasma levels of VEGF and SDF-1 were measured by enzyme-linked immunosorbent assay. In response to SAT, the levels of both EPC and VEGF/SDF-1 markedly increased (P < .001 vs baseline) but returned to the baseline levels after DSAT. A similar change was observed with the EPC clonogenic potential, but on DSAT the baseline level was incompletely attained.

Conclusions

In response to SAT, patients with chronic heart failure show enhanced EPC levels and clonogenic potential that is mirrored by increased plasma VEGF and SDF-1 levels. DSAT can interfere with the maintenance of training-acquired VEGF/SDF-1-related EPC levels and clonogenic potential.

Section snippets

Study Subjects

Patients with symptomatic CHF in a stable condition were enrolled in this study. The criteria for eligibility were medically stable heart failure in New York Heart Association (NYHA) class II or III for at least 3 months before the study, left ventricular dysfunction with an ejection fraction (EF) of ≤ 40%, and a peak volume of oxygen utilization (VO2) of ≤ 25 mL·kg·min. Exclusion criteria were myocardial infarction or unstable angina within the previous 6 months, aortic stenosis, uncontrolled

Phenotypic Characteristics of Endothelial Progenitor Cells and Investigation Protocol

EPCs selected for this study were grown for 4 days in vitro and are likely to correspond to the “early outgrowth cells” identified by Hur et al.28 They were reactive with Ulex europaeus agglutinin-1 and DiI-LDL. To minimize possible subjectivity, measurements of EPC levels and clonogenicity in patients were performed in a blinded fashion with respect to their respective treatment assignments.

Patient Characteristics

Twenty-four patients were enrolled, 22 of whom completed the protocol. The cause of heart failure was

Discussion

There is a general consensus that after exercise training of various intensity, patients with cardiovascular risk factors,19 coronary artery disease20, 21, 22 and symptomatic peripheral arterial occlusive disease23 improve their repertoire of CD34pos/KDRpos peripheral blood EPCs. This study is the first to report a 251% increase in CD34pos/KDRpos EPC levels in patients with CHF in response to 8 weeks of SAT.

Implementation of CD34pos/KDRpos EPC levels is paralleled by a marked increase in two

Conclusion

SAT increased both EPC levels and EPC clonogenic capacity in patients with CHF, and these changes are associated to VEGF and SDF-1 increments. This study also suggests that 8-week DSAT can interfere with the maintenance of training-acquired EPC levels and clonogenicity.

Limits

This was a proof-of-principle study. Thus, beneficial clinical effects await to be confirmed by a randomized controlled study in which patients are to be homogeneously enrolled according to causes of heart failure, history of disease, medical therapy, gender, and age, and randomly allocated to SAT and control.

Acknowledgments

We thank Alessandra Zottarelli, Claudia Carraro, and Sabrina Milan for their excellent contribution. This work stems from the European Vascular Genomics Network (http://www.evgn.org), a Network of Excellence supported by the European Community's sixth Framework Programme for Research Priority 1 “Life sciences, genomics and biotechnology for health” (Contract N° LSHM-CT-2003-503254), and the Consortium Agreement European Community “Heart Failure and Cardiac Repair,” IP 018630.

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  • Cited by (0)

    Grants and support: This study was supported by Fondazione Cassamarca-Treviso, Fondazione per la ricerca e cura delle malattie cardiovascolari-Mirano, and by Istituto Superiore di Sanità-National Program on Stem Cells.

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