title: Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
abstract: 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.
authors.affiliation: Department of Neurological and Psychiatric Sciences, Thrombosis Center, University of Florence, Florence, Italy. francescapescini@virgilio.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Pescini
authors.forename: Francesca
authors.initials: F
authors.lastname: Cesari
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Cristina
authors.initials: C
authors.lastname: Sarti
authors.forename: Enza
authors.initials: E
authors.lastname: Zicari
authors.forename: Silvia
authors.initials: S
authors.lastname: Bianchi
authors.forename: Maria T
authors.initials: MT
authors.lastname: Dotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Maurizio
authors.initials: M
authors.lastname: Balestrino
authors.forename: Adriano
authors.initials: A
authors.lastname: Enrico
authors.forename: Carlo
authors.initials: C
authors.lastname: Gandolfo
authors.forename: Anna M
authors.initials: AM
authors.lastname: Gori
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
mesh_terms: 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
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers