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Vascular endothelial growth factors and angiopoietins as new players in mastocytosis
Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patie...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266723/ https://www.ncbi.nlm.nih.gov/pubmed/33687603 http://dx.doi.org/10.1007/s10238-021-00693-0 |
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author | Marcella, Simone Petraroli, Angelica Braile, Mariantonia Parente, Roberta Ferrara, Anne Lise Galdiero, Maria Rosaria Modestino, Luca Cristinziano, Leonardo Rossi, Francesca Wanda Varricchi, Gilda Triggiani, Massimo de Paulis, Amato Spadaro, Giuseppe Loffredo, Stefania |
author_facet | Marcella, Simone Petraroli, Angelica Braile, Mariantonia Parente, Roberta Ferrara, Anne Lise Galdiero, Maria Rosaria Modestino, Luca Cristinziano, Leonardo Rossi, Francesca Wanda Varricchi, Gilda Triggiani, Massimo de Paulis, Amato Spadaro, Giuseppe Loffredo, Stefania |
author_sort | Marcella, Simone |
collection | PubMed |
description | Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSA(KIT WT) and ROSA (KIT D816V) and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSA(KIT WT), ROSA(KIT D816V) and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-021-00693-0. |
format | Online Article Text |
id | pubmed-8266723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-82667232021-07-20 Vascular endothelial growth factors and angiopoietins as new players in mastocytosis Marcella, Simone Petraroli, Angelica Braile, Mariantonia Parente, Roberta Ferrara, Anne Lise Galdiero, Maria Rosaria Modestino, Luca Cristinziano, Leonardo Rossi, Francesca Wanda Varricchi, Gilda Triggiani, Massimo de Paulis, Amato Spadaro, Giuseppe Loffredo, Stefania Clin Exp Med Original Article Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSA(KIT WT) and ROSA (KIT D816V) and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSA(KIT WT), ROSA(KIT D816V) and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-021-00693-0. Springer International Publishing 2021-03-09 2021 /pmc/articles/PMC8266723/ /pubmed/33687603 http://dx.doi.org/10.1007/s10238-021-00693-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Marcella, Simone Petraroli, Angelica Braile, Mariantonia Parente, Roberta Ferrara, Anne Lise Galdiero, Maria Rosaria Modestino, Luca Cristinziano, Leonardo Rossi, Francesca Wanda Varricchi, Gilda Triggiani, Massimo de Paulis, Amato Spadaro, Giuseppe Loffredo, Stefania Vascular endothelial growth factors and angiopoietins as new players in mastocytosis |
title | Vascular endothelial growth factors and angiopoietins as new players in mastocytosis |
title_full | Vascular endothelial growth factors and angiopoietins as new players in mastocytosis |
title_fullStr | Vascular endothelial growth factors and angiopoietins as new players in mastocytosis |
title_full_unstemmed | Vascular endothelial growth factors and angiopoietins as new players in mastocytosis |
title_short | Vascular endothelial growth factors and angiopoietins as new players in mastocytosis |
title_sort | vascular endothelial growth factors and angiopoietins as new players in mastocytosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266723/ https://www.ncbi.nlm.nih.gov/pubmed/33687603 http://dx.doi.org/10.1007/s10238-021-00693-0 |
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