Microparticles produced by activated platelets carry a potent and functionally active angiogenic signal in subjects with crohn’s disease

Eleonora Gaetani, Fabio Del Zompo, Margherita Marcantoni, Ilaria Gatto, Igor Giarretta, Angelo Porfidia, Franco Scaldaferri, Lucrezia Laterza, Loris Lopetuso, Antonio Gasbarrini, Roberto Pola

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number2921
JournalInternational Journal of Molecular Sciences
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

microparticles
Platelets
platelets
Crohn Disease
Blood Platelets
Angiopoietin-1
angiogenesis
Fibroblast Growth Factor 2
Angiogenic Proteins
Thrombospondin 1
inhibitors
Platelet Factor 4
Tissue Inhibitor of Metalloproteinase-1
Plasminogen Activator Inhibitor 1
Platelet-Derived Growth Factor
Endothelin-1
Colitis
Coculture Techniques
Epidermal Growth Factor
proteins

Keywords

  • Angiogenesis
  • Crohn’s disease
  • Microparticles

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Microparticles produced by activated platelets carry a potent and functionally active angiogenic signal in subjects with crohn’s disease. / Gaetani, Eleonora; Zompo, Fabio Del; Marcantoni, Margherita; Gatto, Ilaria; Giarretta, Igor; Porfidia, Angelo; Scaldaferri, Franco; Laterza, Lucrezia; Lopetuso, Loris; Gasbarrini, Antonio; Pola, Roberto.

In: International Journal of Molecular Sciences, Vol. 19, No. 10, 2921, 01.10.2018.

Research output: Contribution to journalArticle

Gaetani, Eleonora ; Zompo, Fabio Del ; 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. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 10.
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AU - Gatto, Ilaria

AU - Giarretta, Igor

AU - Porfidia, Angelo

AU - Scaldaferri, Franco

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AB - 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.

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