Bone Marrow-Derived Progenitor Cells in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

• Published in: Stroke (1970) Vol. 41; no. 2; pp. 218 - 223
• Main Authors: PESCINI, Francesca, CESARI, Francesca, GANDOLFO, Carlo, GORI, Anna M, ABBATE, Rosanna, PANTONI, Leonardo, INZITARI, Domenico, GIUSTI, Betti, SARTI, Cristina, ZICARI, Enza, BIANCHI, Silvia, DOTTI, Maria T, FEDERICO, Antonio, BALESTRINO, Maurizio, ENRICO, Adriano
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-02-2010
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Surface - metabolism; Biological and medical sciences; Biomarkers; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; CADASIL - pathology; CADASIL - physiopathology; Cell Count; Cerebral Arteries - immunology; Cerebral Arteries - pathology; Cerebral Arteries - physiopathology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Dementia - pathology; Dementia - physiopathology; Down-Regulation - physiology; Endothelial Cells - cytology; Endothelial Cells - immunology; Endothelial Cells - metabolism; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Immunophenotyping; Male; Medical sciences; Middle Aged; Neurology; Stem Cells - cytology; Stem Cells - immunology; Stem Cells - metabolism; Stroke - pathology; Stroke - physiopathology; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; Stroke; Nervous system diseases; small vessel; Cardiovascular disease; progenitor cells; Cerebral disorder; Vascular disease; Phenotype; CADASIL; Central nervous system disease; CADASIL syndrome; Bone marrow; Endothelial dysfunction; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.109.563726

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.
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.
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.
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.