Clinical TrialEffects of Exercise Training on Endothelial Progenitor Cells in Patients With Chronic Heart Failure
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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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.