Increased levels of circulating endothelial progenitor cells in patients with Moyamoya disease
Neysan Rafat1, Grietje Ch Beck, Pablo G Peña-Tapia
1Department of Anaesthesiology, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Background And Purpose:
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.
Insights
Moyamoya disease (MMD) patients show higher circulating endothelial progenitor cells, potentially explaining their enhanced blood vessel growth. This mobilization may not solely depend on vascular endothelial growth factor or granulocyte-macrophage colony-stimulating factor.
Area of Science:
- Neuroscience
- Vascular Biology
- Regenerative Medicine
Background:
- Chronic cerebral ischemia increases stroke risk due to poor collateralization.
- Moyamoya disease (MMD) patients exhibit robust arteriogenesis and angiogenesis despite similar stroke risks.
- The mechanisms behind MMD's enhanced vascularization remain unclear.
Purpose of the Study:
- To investigate the mobilization of circulating endothelial progenitor cells (CEPCs) in MMD patients.
- To compare CEPC levels in MMD patients with those in atherosclerotic cerebrovascular disease and healthy controls.
Main Methods:
- Peripheral blood mononuclear cells were isolated from 20 MMD patients, 8 atherosclerotic cerebrovascular disease patients, and 15 healthy controls.
- CEPCs were identified using triple staining for CD133, CD34, and vascular endothelial growth factor receptor-2.
- Serum levels of vascular endothelial growth factor (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured.
Main Results:
- MMD patients had significantly higher CEPC numbers compared to controls and atherosclerotic patients.
- Serum VEGF and GM-CSF levels were elevated in MMD and atherosclerotic patients versus controls.
- An inverse correlation was observed between CEPC numbers and VEGF levels in MMD patients.
Conclusions:
- Increased CEPC numbers in MMD may contribute to enhanced arteriogenesis and angiogenesis.
- CEPC mobilization in MMD appears to be influenced by factors beyond VEGF and GM-CSF.
