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Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects
Eleonora Gaetani1, Fabio Del Zompo2, Margherita Marcantoni3
1Division of Internal Medicine and Gastroenterology, Department of Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy. eleonora.gaetani@unicatt.it.
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.
Insights
Platelet microparticles (MPs) from Crohn's disease (CD) patients carry more angiogenic factors. These MPs promote blood vessel growth, suggesting a new mechanism in CD inflammation with therapeutic potential.
Area of Science:
- Biomedical Science
- Molecular Biology
- Immunology
Background:
- Microparticles (MPs) are vesicles released by cells.
- Activated platelets are a key source of MPs in inflammatory conditions like Crohn's disease (CD).
- Angiogenesis, or new blood vessel formation, is crucial in CD progression.
Purpose of the Study:
- To analyze the angiogenic content of MPs from activated platelets in CD patients.
- To determine if the angiogenic signals in these MPs are functionally active.
Main Methods:
- Isolation and analysis of MPs from activated platelets in CD patients and controls.
- Quantification of angiogenic mRNAs and proteins within MPs.
- In vitro assay using endothelial and interstitial cells to assess angiogenic activity.
Main Results:
- MPs from CD patients showed significantly higher levels of angiogenic mRNAs (EGF, PDGFα, FGF-2, ANGPT1).
- These MPs also contained elevated levels of angiogenic proteins (VEGF, ANGPT1, endoglin, etc.).
- The protein content of these MPs demonstrated functional activity, inducing angiogenesis in vitro.
Conclusions:
- Activated platelet-derived MPs in CD patients are enriched with angiogenic factors.
- These MPs deliver a functionally active angiogenic signal, contributing to inflammation.
- This finding reveals a novel mechanism of angiogenesis in CD with potential therapeutic implications.