Maximal exercise, limb ischemia, and endothelial progenitor cells.
OBJECTIVE
The concept of neovascularization in response to tissue ischemia was recently extended by the finding of postnatal vasculogenesis through circulating endothelial progenitor cells (EPCs). The aim of this study was to assess the role of acute ischemia for EPC mobilization in patients with peripheral arterial occlusive disease (PAOD) and in healthy volunteers.


METHODS
The number of circulating EPCs was analyzed by flow cytometry in PAOD patients (n = 23) with exercise-induced limb ischemia for up to 72 h after a maximal treadmill test and in healthy volunteers (n = 17) who underwent a 15-min suprasystolic occlusion of one lower extremity to induce limb ischemia. Plasma concentrations of vascular endothelial growth factor, basic fibroblast growth factor, tumor necrosis factor-α, and granulocyte macrophage-colony stimulating factor were determined by ELISA.


RESULTS
EPCs (CD 34 pos/KDRpos) increased significantly in both PAOD patients from 82 ± 20 to 256 ± 52 (P < 0.05) and healthy volunteers from 144 ± 39 to 590 ± 61 cells per 1 million events (P < 0.05) in response to induced ischemia, with a maximum after 24 h and returned to baseline within 72 h. The relative increase in EPC numbers was significantly lower in patients with PAOD as compared with healthy volunteers (P < 0.05). Plasma levels of vascular endothelial growth factor increased from 27.4 ± 3.1 to 126.4 ± 12 pg/ml in patients with PAOD (P < 0.05) and from 30.7 ± 6.1 to 134.1 ± 12.4 pg/ml in healthy volunteers (P < 0.05).


CONCLUSIONS
Both patients with symptomatic PAOD and healthy volunteers respond to a single episode of limb ischemia with a time-dependent increase in circulating EPCs. The increase of EPC numbers in response to ischemia is reduced when vascular disease is present, underlining the reduced vasculogenic potential of patients with PAOD.
Sandri
Marcus
M
Department of Internal Medicine/Cardiology, University of Leipzig, Heart-Center, Leipzig, Germany.
Beck
Ephraim Bernhard
EB
Adams
Volker
V
Gielen
Stephan
S
Lenk
Karsten
K
Höllriegel
Robert
R
Mangner
Norman
N
Linke
Axel
A
Erbs
Sandra
S
Möbius-Winkler
Sven
S
Scheinert
Dierk
D
Hambrecht
Rainer
R
Schuler
Gerhard
G
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005434:Flow Cytometry; D005858:Germany; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D058729:Peripheral Arterial Disease / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D011446:Prospective Studies; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014111:Tourniquets; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor