Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia.
OBJECTIVE
The concept of neovascularization in response to tissue ischemia has been extended by the finding of postnatal vasculogenesis initiated by endothelial progenitor cells (EPCs). The aim of this study was to analyze whether a maximal stress test in patients with coronary artery disease (CAD) increases the number of circulating EPCs.


RESULTS
Blood concentration of EPCs was analyzed by FACS and cell culture assay in CAD patients with (n=16) or without (n=12) exercise-induced myocardial ischemia and in healthy subjects (n=11) for up to 144 hours after maximal stress test. Plasma concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor were determined by ELISA. EPCs increased significantly in ischemic patients, with a maximum after 24 to 48 hours (cell culture: 3.3+/-0.5-fold increase; FACS: 3.1+/-0.6-fold increase) and returned to baseline within 72 hour. In nonischemic patients and healthy subjects, no EPC increase was detectable. VEGF levels in ischemic patients increased significantly after 2 to 6 hours (maximum after 2 hours; 4.0+/-1.1-fold increase) and no change was observed in nonischemic patients and healthy subjects; DeltaVEGF and DeltaEPC correlated significantly (r=0.66).


CONCLUSIONS
Patients with symptomatic CAD respond to a single episode of exercise-induced myocardial ischemia with a time-dependent increase in circulating EPCs. This increase may be related to and preceded by an increase in plasma VEGF.
University Leipzig, Heart Center Leipzig, Germany. adav@medizin.uni-leipzig.de
Volker
V
Adams
Karsten
K
Lenk
Axel
A
Linke
Dominik
D
Lenz
Sandra
S
Erbs
Markus
M
Sandri
Attila
A
Tarnok
Stephan
S
Gielen
Frank
F
Emmrich
Gerhard
G
Schuler
Rainer
R
Hambrecht
D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000209:etiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D005080:Exercise Test; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000209:etiology / Q000473:pathology / Q000601:surgery; D009204:Myocardial Revascularization; D005082:Physical Exertion / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor