Increased levels of circulating endothelial progenitor cells in patients with Moyamoya disease.
OBJECTIVE
Chronic cerebral ischemia leads to higher risk for strokes attributable to insufficient collateralization, resulting from inadequate capacity for arteriogenesis and angiogenesis. Patients with Moyamoya disease (MMD) have similar transient ischemic attack frequencies compared to patients with chronic cerebral ischemia with other etiologies, but a strong capacity for arteriogenesis and angiogenesis. The mechanisms involved in the upregulation of the arteriogenesis and angiogenesis in MMD still remain unknown. In the present study we investigated if circulating endothelial progenitor cells are increasingly mobilized during MMD.


METHODS
Twenty MMD patients, 8 patients with atherosclerotic cerebrovascular disease, and 15 healthy individuals were included in this study. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and circulating endothelial progenitor cells were characterized by triple staining using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2. Serum concentrations of vascular endothelial growth factor and granulocyte-macrophage colony-stimulating factor were determined by enzyme-linked immunosorbent assay.


RESULTS
In MMD patients the number of circulating endothelial progenitor cells was significantly higher than in atherosclerotic cerebrovascular disease patients (P<0.002) and healthy controls (P<0.0001). Serum vascular endothelial growth factor concentrations in MMD patients and in atherosclerotic cerebrovascular disease patients were significantly higher compared to those in healthy controls (P<0.0001). Similar findings were observed for granulocyte-macrophage colony-stimulating factor. An inverse correlation between circulating endothelial progenitor cell numbers and serum levels of vascular endothelial growth factor (r=-0.53; P<0,02) was found in the MMD group.


CONCLUSIONS
Our results show increased circulating endothelial progenitor cell numbers in MMD, which may play a role in the increased arteriogenesis and angiogenesis in MMD. Moreover, our results suggest that increased circulating endothelial progenitor cell mobilization in MMD may not be entirely mediated by vascular endothelial growth factor or granulocyte-macrophage colony-stimulating factor.
Rafat
Neysan
N
Department of Anaesthesiology, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Beck
Grietje Ch
GCh
Peña-Tapia
Pablo G
PG
Schmiedek
Peter
P
Vajkoczy
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D002499:Centrifugation, Density Gradient; D002536:Cerebral Arteries / Q000473:pathology; D002548:Cerebral Revascularization; D042783:Endothelial Cells / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D015672:Erythroid Precursor Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis; D002537:Intracranial Arteriosclerosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009072:Moyamoya Disease / Q000473:pathology* / Q000601:surgery; D009389:Neovascularization, Pathologic / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D055815:Young Adult
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor