Increase of circulating endothelial cells in patients with Hereditary Hemorrhagic Telangiectasia

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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.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalInternational Journal of Hematology
Volume101
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Hereditary Hemorrhagic Telangiectasia
Vascular Endothelial Growth Factor Receptor-2
Endothelial Cells
Hematopoietic Stem Cells
Mutation Rate
Vascular Malformations
Age of Onset
Genes
Blood Cells
Healthy Volunteers
Mutation

Keywords

  • ACVRL1
  • CD34<sup>+</sup>CD133<sup>+</sup>VEGFR-2<sup>−</sup> cells
  • CD34<sup>+</sup>VEGFR-2<sup>+</sup> cells
  • Circulating CD34<sup>+</sup> cell
  • ENG
  • Hereditary Hemorrhagic Telangiectasia

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

@article{74a830245c8841e29a95e1d352493c51,
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.",
keywords = "ACVRL1, CD34<sup>+</sup>CD133<sup>+</sup>VEGFR-2<sup>−</sup> cells, CD34<sup>+</sup>VEGFR-2<sup>+</sup> cells, Circulating CD34<sup>+</sup> cell, ENG, Hereditary Hemorrhagic Telangiectasia",
author = "Margherita Massa and Cecilia Canzonieri and Rita Campanelli and Federica Ornati and Gabriela Fois and Fabio Pagella and Elina Matti and Elisabetta Buscarini and Cesare Danesino and Vittorio Rosti and Carla Olivieri",
year = "2014",
doi = "10.1007/s12185-014-1698-4",
language = "English",
volume = "101",
pages = "23--31",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",
number = "1",

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TY - JOUR

T1 - Increase of circulating endothelial cells in patients with Hereditary Hemorrhagic Telangiectasia

AU - Massa, Margherita

AU - Canzonieri, Cecilia

AU - Campanelli, Rita

AU - Ornati, Federica

AU - Fois, Gabriela

AU - Pagella, Fabio

AU - Matti, Elina

AU - Buscarini, Elisabetta

AU - Danesino, Cesare

AU - Rosti, Vittorio

AU - Olivieri, Carla

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - ACVRL1

KW - CD34<sup>+</sup>CD133<sup>+</sup>VEGFR-2<sup>−</sup> cells

KW - CD34<sup>+</sup>VEGFR-2<sup>+</sup> cells

KW - Circulating CD34<sup>+</sup> cell

KW - ENG

KW - Hereditary Hemorrhagic Telangiectasia

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U2 - 10.1007/s12185-014-1698-4

DO - 10.1007/s12185-014-1698-4

M3 - Article

C2 - 25465912

AN - SCOPUS:84925498905

VL - 101

SP - 23

EP - 31

JO - International Journal of Hematology

JF - International Journal of Hematology

SN - 0925-5710

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