TY - JOUR
T1 - Bone marrow-derived progenitor cells in cérébral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
AU - Pescini, Francesca
AU - Cesari, Francesca
AU - Giusti, Betti
AU - Sarti, Cristina
AU - Zicari, Enza
AU - Bianchi, Silvia
AU - Dotti, Maria T.
AU - Federico, Antonio
AU - Balestrino, Maurizio
AU - Enrico, Adriano
AU - Gandolfo, Carlo
AU - Gori, Anna M.
AU - Abbate, Rosanna
AU - Pantoni, Leonardo
AU - Inzitari, Domenico
PY - 2010/2
Y1 - 2010/2
N2 - Background and Purpose-Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease due to cérébral 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/μL, P=0.005; CD133/KDR: 0.07 versus 0.1 cells/μL, P=0.006; CD34/CD133/KDR: 0.05 versus 0.1 cells/μL, 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/μL, P=0.007; CD133: 1.40 versus 2.82 cells/μL, P=0.004; CD34/CD133: 1.44 versus 2.75 cells/μL, 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.
AB - Background and Purpose-Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease due to cérébral 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/μL, P=0.005; CD133/KDR: 0.07 versus 0.1 cells/μL, P=0.006; CD34/CD133/KDR: 0.05 versus 0.1 cells/μL, 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/μL, P=0.007; CD133: 1.40 versus 2.82 cells/μL, P=0.004; CD34/CD133: 1.44 versus 2.75 cells/μL, 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.
KW - CADASIL
KW - Endothelial dysfunction
KW - Phenotype
KW - Progenitor cells
KW - Small vessel
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U2 - 10.1161/STROKEAHA.109.563726
DO - 10.1161/STROKEAHA.109.563726
M3 - Article
C2 - 20035077
AN - SCOPUS:77449134478
VL - 41
SP - 218
EP - 223
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 2
ER -