REVIEW article
Front. Mol. Biosci.
Sec. Molecular Recognition
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1636893
The role of protease-activated receptors (PARs) in the functioning of platelets and platelet-derived microparticles (PMPs)
Provisionally accepted
Urszula Jakobsche-Policht
Agnieszka Bronowicka-Szydełko*Rajmund AdamiecDorota Bednarska-ChabowskaMagdalena Mierzchała-Pasierb
Lukasz LewandowskiKinga Gostomska-PampuchJoanna Adamiec-MroczekMaciej RabczyńskiEdwin KuźnikPaweł LubienieckiOlgierd Dróżdż
Helena MartynowiczAnna KwiecieńMałgorzata StrzeleckaDawid RudkiewiczMarcin PiersiakMaciej ZiomekMikołaj Kondracki
Zuzanna Galińska
Katarzyna Madziarska- Wroclaw Medical University, Wrocław, Poland
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, present on the surface of platelets and platelet-derived microparticles (PMPs), belong to a superfamily of membrane receptors that play a key role in initiating intracellular G protein-dependent signaling pathways. Although four types of PARs have been identified -PAR-1, PAR-2, PAR-3, and PAR-4their mechanisms and functions remain poorly understood. Nevertheless, they are considered promising therapeutic and diagnostic targets, as they play crucial roles in initiating and promoting processes such as coagulation, inflammatory responses, and vascular function. PAR-1 is expressed on various cell types, including endothelial cells, platelets, neurons, and immune cells. Its activation by thrombin initiates a G protein-dependent signaling cascade that stimulates the expression of cytokines, selectins, adhesion molecules, and growth factors. In addition to thrombin, PAR-1 can also be activated by activated protein C (APC) and matrix metalloproteinase-1 (MMP-1). APC triggers cytoprotective signaling pathways, while MMP-1 influences cellular dynamics through alternative signaling mechanisms. PAR-1 activation is also affected by epigenetic modifications and genetic polymorphisms in the PAR-1 gene. Variants such as -1426 C/T and -506 I/D influence receptor expression and are associated with an increased risk of thrombosis, potentially due to epigenetic changes linked to atherosclerosis. The complex signaling network of PAR-1 makes it a promising therapeutic target for the treatment of cardiovascular diseases,
Keywords: Atherosclerosis, Hemostasis, Platelet-derived microparticles, protease-activated receptor (PAR-1, Vessels
Received: 03 Jun 2025; Accepted: 17 Aug 2025.
Copyright: © 2025 Jakobsche-Policht, Bronowicka-Szydełko, Adamiec, Bednarska-Chabowska, Mierzchała-Pasierb, Lewandowski, Gostomska-Pampuch, Adamiec-Mroczek, Rabczyński, Kuźnik, Lubieniecki, Dróżdż, Martynowicz, Kwiecień, Strzelecka, Rudkiewicz, Piersiak, Ziomek, Kondracki, Galińska and Madziarska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Agnieszka Bronowicka-Szydełko, Wroclaw Medical University, Wrocław, Poland
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