title: Increase of circulating endothelial cells in patients with Hereditary Hemorrhagic Telangiectasia.
abstract: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular malformations. The genes known to be associated with HHT include ENG (HHT1), ACVRL1 (HHT2) and SMAD4 (JPHT). It has been reported that circulating CD34(+) cell subsets repair damaged vessels. To investigate whether mobilization of these cells is present in the peripheral blood (PB) of HTT patients, we analyzed CD34(+) cells, CD34(+)VEGFR-2(+) progenitor or mature endothelial cells, and CD34(+)CD133(+)VEGFR-2(-) hematopoietic progenitor cells (HPCs). Cytofluorimetric analysis was performed in 150 HTT patients and 43 healthy subjects (CTRLs). In HTT patients, PB CD34(+) cells were significantly increased; the frequency of endothelial cells was higher (P = 0.002), while the frequency of CD34(+)CD133(+)VEGFR-2(-) HPCs was lower (P = 0.00007) than in CTRLs. Results were comparable in patients with ENG or ACVRL1 gene mutation; in patients with ENG mutation, the frequency of the cell subsets inversely correlated with the age of the patients at time of sampling (CD34(+)), disease duration (CD34(+)VEGFR-2(+)), and age at disease onset (CD34(+)CD133(+) VEGFR-2(-)). In conclusion, HHT patients show an increase of circulating endothelial cells and a decrease of HPCs. In patients with ENG mutation, the frequency of CD34(+) endothelial cells correlates with specific clinical characteristics suggesting that their active turnover characterizes the initial phase of the disease.
authors.affiliation: Laboratori Sperimentali di Ricerca Area Biotecnologie, IRCCS Fondazione "Policlinico S. Matteo", Viale Golgi 19, 27100, Pavia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Cecilia
authors.initials: C
authors.lastname: Canzonieri
authors.forename: Rita
authors.initials: R
authors.lastname: Campanelli
authors.forename: Federica
authors.initials: F
authors.lastname: Ornati
authors.forename: Gabriela
authors.initials: G
authors.lastname: Fois
authors.forename: Fabio
authors.initials: F
authors.lastname: Pagella
authors.forename: Elina
authors.initials: E
authors.lastname: Matti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Buscarini
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.forename: Carla
authors.initials: C
authors.lastname: Olivieri
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II