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.
Highlights
Microparticles (MPs) are a type of extracellular vesicle produced by cells upon activation, stimulation, and death, through budding of the plasma membrane, formation of membrane “blebs”, and eventual release into the bloodstream [1]
We found that aPMPs are increased in the plasma of subjects with active Crohn’s disease (CD), compared to healthy subjects (HS) and subjects with inactive CD, and their number correlates with the diseases’ activity and C-reactive protein (CRP) levels
CRP was significantly higher in the active CD (aCD) group compared to both subjects with inactive CD (iCD) and HS (p < 0.01)
Summary
Microparticles (MPs) are a type of extracellular vesicle produced by cells upon activation, stimulation, and death, through budding of the plasma membrane, formation of membrane “blebs”, and eventual release into the bloodstream [1]. A number of studies have demonstrated higher numbers of circulating MPs in subjects with inflammatory diseases, including Crohn’s disease (CD) [5–8]. These studies have mainly focused on the quantification of MPs and the analysis of certain specific MP functional properties, such as the ability to bind annexin. We analyzed the number and angiogenic content of MPs produced by activated platelets (aPMPs) circulating in the bloodstream of subjects with CD. In subjects with aCD, aPMPs carry high levels of angiogenic mRNAs and proteins This content is functionally active, since it is able to induce angiogenesis in vitro
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
