Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
OBJECTIVE
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.
Pescini
Francesca
F
Department of Neurological and Psychiatric Sciences, Thrombosis Center, University of Florence, Florence, Italy. francescapescini@virgilio.it
Cesari
Francesca
F
Giusti
Betti
B
Sarti
Cristina
C
Zicari
Enza
E
Bianchi
Silvia
S
Dotti
Maria T
MT
Federico
Antonio
A
Balestrino
Maurizio
M
Enrico
Adriano
A
Gandolfo
Carlo
C
Gori
Anna M
AM
Abbate
Rosanna
R
Pantoni
Leonardo
L
Inzitari
Domenico
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D046589:CADASIL / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D002536:Cerebral Arteries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D003704:Dementia / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D020521:Stroke / Q000473:pathology / Q000503:physiopathology
D000954:Antigens, Surface; D015415:Biomarkers