Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps

Neutrophil extracellular traps (NETs) have received significant attention in recent years for their role in both the immune response and the vascular damage associated with inflammation. Platelets have been described as critical components of NETs since the initial description of this physio-patholo...

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Main Authors: Christopher Sennett, Giordano Pula
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/5/335
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author Christopher Sennett
Giordano Pula
author_facet Christopher Sennett
Giordano Pula
author_sort Christopher Sennett
collection DOAJ
description Neutrophil extracellular traps (NETs) have received significant attention in recent years for their role in both the immune response and the vascular damage associated with inflammation. Platelets have been described as critical components of NETs since the initial description of this physio-pathological response of neutrophils. Platelets have been shown to play a dual role as responders and also as stimulators of NETs. The direct interaction with DNA leads to the entrapment of platelets into NETs, a phenomenon that significantly contributes to the thrombotic complications of inflammation and neutrophil activation, while the direct and paracrine stimulation of neutrophils by platelets has been shown to initiate the process of NET formation. In this review, we provide a comprehensive description of our current understanding of the molecular mechanisms underlying the entrapping of platelets into NETs and, in parallel, the platelet-driven cellular responses promoting NET formation. We then illustrate established examples of the contribution of NETs to vascular pathologies, describe the important questions that remain to be answered regarding the contribution of platelets to NET formation and NET-dependent cardiovascular complication, and highlight the fundamental steps taken towards the application of our understanding of platelets’ contribution to NETs for the development of novel cardiovascular therapies.
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spelling doaj-art-a22d4ac90ecc4a4db06ed907e227b87b2025-08-20T02:58:58ZengMDPI AGCells2073-44092025-02-0114533510.3390/cells14050335Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular TrapsChristopher Sennett0Giordano Pula1Biomedical Institute for Multimorbidity (BIM), Hull York Medical School (HYMS), University of Hull, Hull HU6 7RX, UKBiomedical Institute for Multimorbidity (BIM), Hull York Medical School (HYMS), University of Hull, Hull HU6 7RX, UKNeutrophil extracellular traps (NETs) have received significant attention in recent years for their role in both the immune response and the vascular damage associated with inflammation. Platelets have been described as critical components of NETs since the initial description of this physio-pathological response of neutrophils. Platelets have been shown to play a dual role as responders and also as stimulators of NETs. The direct interaction with DNA leads to the entrapment of platelets into NETs, a phenomenon that significantly contributes to the thrombotic complications of inflammation and neutrophil activation, while the direct and paracrine stimulation of neutrophils by platelets has been shown to initiate the process of NET formation. In this review, we provide a comprehensive description of our current understanding of the molecular mechanisms underlying the entrapping of platelets into NETs and, in parallel, the platelet-driven cellular responses promoting NET formation. We then illustrate established examples of the contribution of NETs to vascular pathologies, describe the important questions that remain to be answered regarding the contribution of platelets to NET formation and NET-dependent cardiovascular complication, and highlight the fundamental steps taken towards the application of our understanding of platelets’ contribution to NETs for the development of novel cardiovascular therapies.https://www.mdpi.com/2073-4409/14/5/335neutrophil extracellular trapNETNETosisplatelet
spellingShingle Christopher Sennett
Giordano Pula
Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps
Cells
neutrophil extracellular trap
NET
NETosis
platelet
title Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps
title_full Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps
title_fullStr Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps
title_full_unstemmed Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps
title_short Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps
title_sort trapped in the nets multiple roles of platelets in the vascular complications associated with neutrophil extracellular traps
topic neutrophil extracellular trap
NET
NETosis
platelet
url https://www.mdpi.com/2073-4409/14/5/335
work_keys_str_mv AT christophersennett trappedinthenetsmultiplerolesofplateletsinthevascularcomplicationsassociatedwithneutrophilextracellulartraps
AT giordanopula trappedinthenetsmultiplerolesofplateletsinthevascularcomplicationsassociatedwithneutrophilextracellulartraps