Impairment of circulating endothelial progenitors in Down syndrome

Valerio Costa, Linda Sommese, Amelia Casamassimi, Roberta Colicchio, Claudia Angelini, Valentina Marchesano, Lara Milone, Bartolomeo Farzati, Alfonso Giovane, Carmela Fiorito, Monica Rienzo, Marco Picardi, Bice Avallone, Massimiliano Marco Corsi, Berardo Sarubbi, Raffaele Calabr, Paola Salvatore, Alfredo Ciccodicola, Claudio Napoli

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background. Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods. Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1 plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results. We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1 plasma levels and their progenitors had a reduced expression of SDF-1 encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions. Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.

Original languageEnglish
Article number40
JournalBMC Medical Genomics
Volume3
DOIs
Publication statusPublished - 2010

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Down Syndrome
Oxidative Stress
Stem Cells
Hydrogen Peroxide
Genes
Infection
Bartonella henselae
Pathologic Neovascularization
Chromosomes, Human, Pair 21
Microarray Analysis
Transmission Electron Microscopy
Cell Size
Disease Progression
Enzyme-Linked Immunosorbent Assay
Inflammation
Gene Expression
Polymerase Chain Reaction
Membranes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Costa, V., Sommese, L., Casamassimi, A., Colicchio, R., Angelini, C., Marchesano, V., ... Napoli, C. (2010). Impairment of circulating endothelial progenitors in Down syndrome. BMC Medical Genomics, 3, [40]. https://doi.org/10.1186/1755-8794-3-40

Impairment of circulating endothelial progenitors in Down syndrome. / Costa, Valerio; Sommese, Linda; Casamassimi, Amelia; Colicchio, Roberta; Angelini, Claudia; Marchesano, Valentina; Milone, Lara; Farzati, Bartolomeo; Giovane, Alfonso; Fiorito, Carmela; Rienzo, Monica; Picardi, Marco; Avallone, Bice; Marco Corsi, Massimiliano; Sarubbi, Berardo; Calabr, Raffaele; Salvatore, Paola; Ciccodicola, Alfredo; Napoli, Claudio.

In: BMC Medical Genomics, Vol. 3, 40, 2010.

Research output: Contribution to journalArticle

Costa, V, Sommese, L, Casamassimi, A, Colicchio, R, Angelini, C, Marchesano, V, Milone, L, Farzati, B, Giovane, A, Fiorito, C, Rienzo, M, Picardi, M, Avallone, B, Marco Corsi, M, Sarubbi, B, Calabr, R, Salvatore, P, Ciccodicola, A & Napoli, C 2010, 'Impairment of circulating endothelial progenitors in Down syndrome', BMC Medical Genomics, vol. 3, 40. https://doi.org/10.1186/1755-8794-3-40
Costa V, Sommese L, Casamassimi A, Colicchio R, Angelini C, Marchesano V et al. Impairment of circulating endothelial progenitors in Down syndrome. BMC Medical Genomics. 2010;3. 40. https://doi.org/10.1186/1755-8794-3-40
Costa, Valerio ; Sommese, Linda ; Casamassimi, Amelia ; Colicchio, Roberta ; Angelini, Claudia ; Marchesano, Valentina ; Milone, Lara ; Farzati, Bartolomeo ; Giovane, Alfonso ; Fiorito, Carmela ; Rienzo, Monica ; Picardi, Marco ; Avallone, Bice ; Marco Corsi, Massimiliano ; Sarubbi, Berardo ; Calabr, Raffaele ; Salvatore, Paola ; Ciccodicola, Alfredo ; Napoli, Claudio. / Impairment of circulating endothelial progenitors in Down syndrome. In: BMC Medical Genomics. 2010 ; Vol. 3.
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AU - Costa, Valerio

AU - Sommese, Linda

AU - Casamassimi, Amelia

AU - Colicchio, Roberta

AU - Angelini, Claudia

AU - Marchesano, Valentina

AU - Milone, Lara

AU - Farzati, Bartolomeo

AU - Giovane, Alfonso

AU - Fiorito, Carmela

AU - Rienzo, Monica

AU - Picardi, Marco

AU - Avallone, Bice

AU - Marco Corsi, Massimiliano

AU - Sarubbi, Berardo

AU - Calabr, Raffaele

AU - Salvatore, Paola

AU - Ciccodicola, Alfredo

AU - Napoli, Claudio

PY - 2010

Y1 - 2010

N2 - Background. Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods. Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1 plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results. We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1 plasma levels and their progenitors had a reduced expression of SDF-1 encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions. Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.

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