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Published on: June 14, 2017
Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and
Francesca Pescini1, Francesca Cesari, Betti Giusti
1Department of Neurological and Psychiatric Sciences, Thrombosis Center, University of Florence, Florence, Italy. francescapescini@virgilio.it
Insights
Patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) have significantly lower levels of endothelial progenitor cells. Circulating progenitor cells (CPCs) were reduced in CADASIL patients with stroke or dementia, correlating with cognitive and motor performance.
Area of Science:
- Neuroscience
- Vascular Biology
- Regenerative Medicine
Background:
- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic small vessel disease causing stroke and cognitive decline.
- The precise mechanisms linking vascular changes to brain damage in CADASIL are not fully understood, with endothelial dysfunction being a key hypothesis.
- Endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) are crucial for maintaining vascular health and repair.
Purpose of the Study:
- To investigate the role of endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) in CADASIL.
- To determine if levels of these progenitor cells differ between CADASIL patients and healthy controls.
- To explore the association between progenitor cell levels and clinical manifestations in CADASIL.
Main Methods:
- Flow cytometry was used to quantify EPCs and CPCs in the peripheral blood of 29 CADASIL patients and 29 age- and sex-matched controls.
- EPCs were identified as CD34/KDR, CD133/KDR, and CD34/CD133/KDR positive cells.
- CPCs were identified as CD34, CD133, and CD34/CD133 positive cells.
Main Results:
- Patients with CADASIL exhibited significantly lower levels of all measured endothelial progenitor cell (EPC) subtypes compared to controls.
- Circulating progenitor cell (CPC) levels were not significantly different in CADASIL overall, but were markedly reduced in patients with stroke or dementia.
- Reduced CPC levels correlated significantly with poorer cognitive and motor performance measures in CADASIL patients.
Conclusions:
- This study demonstrates a significant association between reduced endothelial progenitor cells and CADASIL.
- The findings support the hypothesis of endothelial dysfunction playing a role in CADASIL pathogenesis.
- Circulating progenitor cell levels may serve as a biomarker for disease severity and clinical outcomes in CADASIL.
Background And Purpose:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease due to cerebral microangiopathy presenting with variable pictures, including stroke, progressive cognitive impairment, and disability. Mechanisms leading from vessel structural changes to parenchymal damage and eventually to clinical expression are not fully understood. Among pathogenic processes, endothelial dysfunction has been hypothesized. Endothelial progenitor cells and circulating progenitor cells (CPCs) derived from bone marrow participate in endothelium structure and function maintenance and contribute to ischemic area revascularization. No data are available about these cells in CADASIL. Our objective in this study was to evaluate endothelial progenitor cells and CPCs role in CADASIL.
Methods:
Twenty-nine patients with CADASIL and 29 sex- and age-matched control subjects were enrolled. Cells were measured in peripheral blood using flow cytometry. Endothelial progenitor cells were defined as positive for CD34/KDR, CD133/KDR, and CD34/CD133/KDR; and CPCs as positive for CD34, CD133, and CD34/CD133.
Results:
Endothelial progenitor cells were significantly lower in patients with CADASIL than in control subjects (CD34/KDR: 0.05 versus 0.1 cells/microL, P=0.005; CD133/KDR: 0.07 versus 0.1 cells/microL, P=0.006; CD34/CD133/KDR: 0.05 versus 0.1 cells/microL, P=0.001). The difference remained significant after adjusting for age, sex, and statin use. CPCs were not significantly lower in CADASIL, but patients with stroke or dementia had significantly reduced CPC levels than patients without (CD34: 1.68 versus 2.95 cells/microL, P=0.007; CD133: 1.40 versus 2.82 cells/microL, P=0.004; CD34/CD133: 1.44 versus 2.75 cells/microL, P=0.004). CPC levels significantly correlated with cognitive and motor performance measures.
Conclusions:
We have documented an association between endothelial progenitor cells and CPCs and CADASIL, extending previous data about the presence of endothelial dysfunction in this disease and its potential role in modulating phenotype.
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