Kinetic and Angiogenic Activity of Circulating Endothelial Colony Forming Cells in Patients with Infantile Haemangioma Receiving Propranolol

Research output: Contribution to journalArticle

Abstract

Endothelial progenitor cells (EPCs) have been suggested to contribute to the neovascularization of infantile haemangioma (IH). There is strong evidence of the efficacy of propranolol in the treatment of IH, possibly by inhibiting both vasculogenesis and angiogenesis in the tumour. We evaluate the frequency of circulating endothelial colony forming cells (ECFCs), as the best EPC surrogate, in patients with IH at diagnosis and while receiving propranolol by an ex vivo 12-month longitudinal study. Biological aspects of the ECFCs, such as their in vitro angiogenic potential, membrane CXCR4 expression and Ca 2+ signalling, were investigated. Circulating ECFCs were isolated by in vitro culture and expanded for 2 to 3 passages in 23 patients with IH (median age: 5.5 months, range: 5.5 weeks-11 months) before and 3, 6, 9 and 12 months after receiving propranolol. Twenty-four healthy subjects comparable for age were also assessed (CTRLs). Untreated patients with IH had a circulating ECFC frequency lower (p = 0.001) than CTRLs; nevertheless, in in vitro starving conditions, ECFCs showed enhanced capacity to form tube-like structures than those of CTRLs. Patients with IH following the therapy with propranolol had a significantly increased (p = 0.022) circulating ECFC frequency, that showed a diminished tube-like formation capacity in vitro, and an altered constitutive store-operated Ca 2+ entry. ECFCs play a role in IH pathogenesis; the response to propranolol therapy is associated with their increased frequency in the peripheral blood and a reduction of their vasculogenic activity.

Original languageEnglish
Article number180507
Pages (from-to)274-284
Number of pages11
JournalThrombosis and Haemostasis
Volume119
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

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Hemangioma
Propranolol
Membrane Potentials
Longitudinal Studies
Healthy Volunteers
Therapeutics
In Vitro Techniques
Neoplasms

Keywords

  • angiogenesis
  • endothelial colony forming cells
  • endothelial progenitor cells
  • infantile haemangioma
  • propranolol

ASJC Scopus subject areas

  • Hematology

Cite this

@article{556b5bb362c04a30b85204f2a5e5361e,
title = "Kinetic and Angiogenic Activity of Circulating Endothelial Colony Forming Cells in Patients with Infantile Haemangioma Receiving Propranolol",
abstract = "Endothelial progenitor cells (EPCs) have been suggested to contribute to the neovascularization of infantile haemangioma (IH). There is strong evidence of the efficacy of propranolol in the treatment of IH, possibly by inhibiting both vasculogenesis and angiogenesis in the tumour. We evaluate the frequency of circulating endothelial colony forming cells (ECFCs), as the best EPC surrogate, in patients with IH at diagnosis and while receiving propranolol by an ex vivo 12-month longitudinal study. Biological aspects of the ECFCs, such as their in vitro angiogenic potential, membrane CXCR4 expression and Ca 2+ signalling, were investigated. Circulating ECFCs were isolated by in vitro culture and expanded for 2 to 3 passages in 23 patients with IH (median age: 5.5 months, range: 5.5 weeks-11 months) before and 3, 6, 9 and 12 months after receiving propranolol. Twenty-four healthy subjects comparable for age were also assessed (CTRLs). Untreated patients with IH had a circulating ECFC frequency lower (p = 0.001) than CTRLs; nevertheless, in in vitro starving conditions, ECFCs showed enhanced capacity to form tube-like structures than those of CTRLs. Patients with IH following the therapy with propranolol had a significantly increased (p = 0.022) circulating ECFC frequency, that showed a diminished tube-like formation capacity in vitro, and an altered constitutive store-operated Ca 2+ entry. ECFCs play a role in IH pathogenesis; the response to propranolol therapy is associated with their increased frequency in the peripheral blood and a reduction of their vasculogenic activity.",
keywords = "angiogenesis, endothelial colony forming cells, endothelial progenitor cells, infantile haemangioma, propranolol",
author = "Rita Campanelli and Codazzi, {Alessia Claudia} and Valentina Poletto and Carlotta Abb{\`a} and Paolo Catarsi and Gabriela Fois and Avanzini, {Maria Antonietta} and Valeria Brazzelli and Chryssoula Tzialla and {De Silvestri}, Annalisa and Carmine Tinelli and Amelia Licari and Roberto Berra-Romani and Estella Zuccolo and Francesco Moccia and Savina Mannarino and Vittorio Rosti and Margherita Massa",
year = "2019",
month = "1",
day = "1",
doi = "10.1055/s-0038-1676855",
language = "English",
volume = "119",
pages = "274--284",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
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T1 - Kinetic and Angiogenic Activity of Circulating Endothelial Colony Forming Cells in Patients with Infantile Haemangioma Receiving Propranolol

AU - Campanelli, Rita

AU - Codazzi, Alessia Claudia

AU - Poletto, Valentina

AU - Abbà, Carlotta

AU - Catarsi, Paolo

AU - Fois, Gabriela

AU - Avanzini, Maria Antonietta

AU - Brazzelli, Valeria

AU - Tzialla, Chryssoula

AU - De Silvestri, Annalisa

AU - Tinelli, Carmine

AU - Licari, Amelia

AU - Berra-Romani, Roberto

AU - Zuccolo, Estella

AU - Moccia, Francesco

AU - Mannarino, Savina

AU - Rosti, Vittorio

AU - Massa, Margherita

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Endothelial progenitor cells (EPCs) have been suggested to contribute to the neovascularization of infantile haemangioma (IH). There is strong evidence of the efficacy of propranolol in the treatment of IH, possibly by inhibiting both vasculogenesis and angiogenesis in the tumour. We evaluate the frequency of circulating endothelial colony forming cells (ECFCs), as the best EPC surrogate, in patients with IH at diagnosis and while receiving propranolol by an ex vivo 12-month longitudinal study. Biological aspects of the ECFCs, such as their in vitro angiogenic potential, membrane CXCR4 expression and Ca 2+ signalling, were investigated. Circulating ECFCs were isolated by in vitro culture and expanded for 2 to 3 passages in 23 patients with IH (median age: 5.5 months, range: 5.5 weeks-11 months) before and 3, 6, 9 and 12 months after receiving propranolol. Twenty-four healthy subjects comparable for age were also assessed (CTRLs). Untreated patients with IH had a circulating ECFC frequency lower (p = 0.001) than CTRLs; nevertheless, in in vitro starving conditions, ECFCs showed enhanced capacity to form tube-like structures than those of CTRLs. Patients with IH following the therapy with propranolol had a significantly increased (p = 0.022) circulating ECFC frequency, that showed a diminished tube-like formation capacity in vitro, and an altered constitutive store-operated Ca 2+ entry. ECFCs play a role in IH pathogenesis; the response to propranolol therapy is associated with their increased frequency in the peripheral blood and a reduction of their vasculogenic activity.

AB - Endothelial progenitor cells (EPCs) have been suggested to contribute to the neovascularization of infantile haemangioma (IH). There is strong evidence of the efficacy of propranolol in the treatment of IH, possibly by inhibiting both vasculogenesis and angiogenesis in the tumour. We evaluate the frequency of circulating endothelial colony forming cells (ECFCs), as the best EPC surrogate, in patients with IH at diagnosis and while receiving propranolol by an ex vivo 12-month longitudinal study. Biological aspects of the ECFCs, such as their in vitro angiogenic potential, membrane CXCR4 expression and Ca 2+ signalling, were investigated. Circulating ECFCs were isolated by in vitro culture and expanded for 2 to 3 passages in 23 patients with IH (median age: 5.5 months, range: 5.5 weeks-11 months) before and 3, 6, 9 and 12 months after receiving propranolol. Twenty-four healthy subjects comparable for age were also assessed (CTRLs). Untreated patients with IH had a circulating ECFC frequency lower (p = 0.001) than CTRLs; nevertheless, in in vitro starving conditions, ECFCs showed enhanced capacity to form tube-like structures than those of CTRLs. Patients with IH following the therapy with propranolol had a significantly increased (p = 0.022) circulating ECFC frequency, that showed a diminished tube-like formation capacity in vitro, and an altered constitutive store-operated Ca 2+ entry. ECFCs play a role in IH pathogenesis; the response to propranolol therapy is associated with their increased frequency in the peripheral blood and a reduction of their vasculogenic activity.

KW - angiogenesis

KW - endothelial colony forming cells

KW - endothelial progenitor cells

KW - infantile haemangioma

KW - propranolol

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DO - 10.1055/s-0038-1676855

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