Cargando…
Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease
Microparticles (MPs) are submicron vesicles shed from various cell types upon activation, stimulation, and death. Activated platelets are an important source of circulating MPs in subjects with inflammatory diseases, including Crohn’s disease (CD). Angiogenesis is a hallmark of inflammation in CD an...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212893/ https://www.ncbi.nlm.nih.gov/pubmed/30261608 http://dx.doi.org/10.3390/ijms19102921 |
_version_ | 1783367644654600192 |
---|---|
author | Gaetani, Eleonora Del Zompo, Fabio Marcantoni, Margherita Gatto, Ilaria Giarretta, Igor Porfidia, Angelo Scaldaferri, Franco Laterza, Lucrezia Lopetuso, Loris Gasbarrini, Antonio Pola, Roberto |
author_facet | Gaetani, Eleonora Del Zompo, Fabio Marcantoni, Margherita Gatto, Ilaria Giarretta, Igor Porfidia, Angelo Scaldaferri, Franco Laterza, Lucrezia Lopetuso, Loris Gasbarrini, Antonio Pola, Roberto |
author_sort | Gaetani, Eleonora |
collection | PubMed |
description | Microparticles (MPs) are submicron vesicles shed from various cell types upon activation, stimulation, and death. Activated platelets are an important source of circulating MPs in subjects with inflammatory diseases, including Crohn’s disease (CD). Angiogenesis is a hallmark of inflammation in CD and plays an active role in sustaining disease progression, while targeting angiogenesis may be an effective approach to block colitis. In this study, we analyzed the angiogenic content of the MPs produced by activated platelets in subjects with CD. We also evaluated whether the angiogenic signal carried by these MPs was functionally active, or able to induce angiogenesis. We found that, in subjects with CD, MPs produced by activated platelets contain significantly higher levels of angiogenic mRNAs, such as epidermal growth factor (EGF), platelet-derived growth factor-α (PDGFα), fibroblast growth factor (FGF-2), and angiopoietin-1 (ANGPT1), compared to MPs isolated from control subjects. They also contain significantly higher levels of prototypical angiogenic proteins, including vascular endothelial growth factor (VEGF), angiopoietin-1, endoglin, endothelin-1, pentraxin 3, platelet factor-4, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases-1 (TIMP-1), and thrombospondin 1. The protein content of these MPs is functionally active, since it has the ability to induce a robust angiogenic process in an endothelial cell/interstitial cell co-culture in vitro assay. Our results reveal a potential novel mechanism through which the angiogenic signal is delivered in subjects with CD, with potentially important clinical and therapeutic implications. |
format | Online Article Text |
id | pubmed-6212893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62128932018-11-14 Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease Gaetani, Eleonora Del Zompo, Fabio Marcantoni, Margherita Gatto, Ilaria Giarretta, Igor Porfidia, Angelo Scaldaferri, Franco Laterza, Lucrezia Lopetuso, Loris Gasbarrini, Antonio Pola, Roberto Int J Mol Sci Article Microparticles (MPs) are submicron vesicles shed from various cell types upon activation, stimulation, and death. Activated platelets are an important source of circulating MPs in subjects with inflammatory diseases, including Crohn’s disease (CD). Angiogenesis is a hallmark of inflammation in CD and plays an active role in sustaining disease progression, while targeting angiogenesis may be an effective approach to block colitis. In this study, we analyzed the angiogenic content of the MPs produced by activated platelets in subjects with CD. We also evaluated whether the angiogenic signal carried by these MPs was functionally active, or able to induce angiogenesis. We found that, in subjects with CD, MPs produced by activated platelets contain significantly higher levels of angiogenic mRNAs, such as epidermal growth factor (EGF), platelet-derived growth factor-α (PDGFα), fibroblast growth factor (FGF-2), and angiopoietin-1 (ANGPT1), compared to MPs isolated from control subjects. They also contain significantly higher levels of prototypical angiogenic proteins, including vascular endothelial growth factor (VEGF), angiopoietin-1, endoglin, endothelin-1, pentraxin 3, platelet factor-4, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases-1 (TIMP-1), and thrombospondin 1. The protein content of these MPs is functionally active, since it has the ability to induce a robust angiogenic process in an endothelial cell/interstitial cell co-culture in vitro assay. Our results reveal a potential novel mechanism through which the angiogenic signal is delivered in subjects with CD, with potentially important clinical and therapeutic implications. MDPI 2018-09-26 /pmc/articles/PMC6212893/ /pubmed/30261608 http://dx.doi.org/10.3390/ijms19102921 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gaetani, Eleonora Del Zompo, Fabio Marcantoni, Margherita Gatto, Ilaria Giarretta, Igor Porfidia, Angelo Scaldaferri, Franco Laterza, Lucrezia Lopetuso, Loris Gasbarrini, Antonio Pola, Roberto Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease |
title | Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease |
title_full | Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease |
title_fullStr | Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease |
title_full_unstemmed | Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease |
title_short | Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn’s Disease |
title_sort | microparticles produced by activated platelets carry a potent and functionally active angiogenic signal in subjects with crohn’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212893/ https://www.ncbi.nlm.nih.gov/pubmed/30261608 http://dx.doi.org/10.3390/ijms19102921 |
work_keys_str_mv | AT gaetanieleonora microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT delzompofabio microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT marcantonimargherita microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT gattoilaria microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT giarrettaigor microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT porfidiaangelo microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT scaldaferrifranco microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT laterzalucrezia microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT lopetusoloris microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT gasbarriniantonio microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease AT polaroberto microparticlesproducedbyactivatedplateletscarryapotentandfunctionallyactiveangiogenicsignalinsubjectswithcrohnsdisease |