Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies.
BACKGROUND
Exercise training (ET) has been shown to improve regional perfusion in ischemic syndromes. This might be partially related to a regeneration of diseased endothelium by circulating progenitor cells (CPCs) or CPC-derived vasculogenesis. The aim of the present study was to determine whether ischemic stimuli during ET are required to promote CPC mobilization in patients with cardiovascular diseases.


RESULTS
Patients with peripheral arterial occlusive disease (PAOD) were randomized to 4 weeks of daily ischemic ET or control (group A). Successfully revascularized patients with PAOD were randomized to 4 weeks of daily nonischemic ET or control (group B). Patients with stable coronary artery disease were subjected to 4 weeks of subischemic ET or control (group C). At baseline and after 4 weeks, the number of KDR+/CD34+ CPCs was determined by fluorescence-activated cell sorting analysis. Levels of vascular endothelial growth factor (VEGF) were measured by ELISA. A Matrigel assay was used to quantify CPC integration into vascular structures. Expression of the homing factor CXCR4 was determined by reverse transcription-polymerase chain reaction. In group A only, ischemic ET increased VEGF levels by 310% (P<0.05 versus control) associated with an increase in CPCs by 440% (P<0.05 versus control), increased CXCR4 expression, and enhanced integration of CPCs into endothelial networks. In contrast, subischemic ET in groups B and C increased CXCR4 expression and CPC integration.


CONCLUSIONS
In training programs, symptomatic tissue ischemia seems to be a prerequisite for CPC mobilization. However, ischemic and subischemic ET programs affect CXCR4 expression of CPCs, which might lead to an improved CPC integration into endothelial networks.
Sandri
Marcus
M
Heart Center, Department of Internal Medicine/Cardiology, University of Leipzig, Leipzig, Germany.
Adams
Volker
V
Gielen
Stephan
S
Linke
Axel
A
Lenk
Karsten
K
Kränkel
Nicolle
N
Lenz
Dominik
D
Erbs
Sandra
S
Scheinert
Dierk
D
Mohr
Friedrich Wilhelm
FW
Schuler
Gerhard
G
Hambrecht
Rainer
R
D000368:Aged; D001157:Arterial Occlusive Diseases / Q000628:therapy*; D002465:Cell Movement; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D005080:Exercise Test; D005081:Exercise Therapy; D006133:Growth Substances / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007511:Ischemia; D019194:Ischemic Preconditioning; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D016491:Peripheral Vascular Diseases / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D006133:Growth Substances; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A