The renin-angiotensin system in healthy human platelets: expressed but inactive

Platelets play a crucial role in arterial thrombus formation, offering potential for new antiplatelet therapies with reduced bleeding risk. Here, we investigated the role of the renin-angiotensin system (RAS) in human platelets and explored its potential link to COVID-19 coagulopathy. Experiments we...

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Main Authors: François Panosetti, François M. Cuenot, Damian S. Saint Auguste, Ana C. Martins Cavaco, Allancer D. C. Nunes, Philip H. J. Lu, Céline Magrini, Max Molot, Gabriel Sanglard, Rodi Günçü, Yassine Zouaghi, Charles Béguelin, Augusto Martins Lima, Nikolaos Stergiopulos
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Platelets
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Online Access:https://www.tandfonline.com/doi/10.1080/09537104.2025.2546982
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author François Panosetti
François M. Cuenot
Damian S. Saint Auguste
Ana C. Martins Cavaco
Allancer D. C. Nunes
Philip H. J. Lu
Céline Magrini
Max Molot
Gabriel Sanglard
Rodi Günçü
Yassine Zouaghi
Charles Béguelin
Augusto Martins Lima
Nikolaos Stergiopulos
author_facet François Panosetti
François M. Cuenot
Damian S. Saint Auguste
Ana C. Martins Cavaco
Allancer D. C. Nunes
Philip H. J. Lu
Céline Magrini
Max Molot
Gabriel Sanglard
Rodi Günçü
Yassine Zouaghi
Charles Béguelin
Augusto Martins Lima
Nikolaos Stergiopulos
author_sort François Panosetti
collection DOAJ
description Platelets play a crucial role in arterial thrombus formation, offering potential for new antiplatelet therapies with reduced bleeding risk. Here, we investigated the role of the renin-angiotensin system (RAS) in human platelets and explored its potential link to COVID-19 coagulopathy. Experiments were performed ex vivo on healthy human platelets. The expression of RAS receptors (Mas, MrgD, ACE, ACE2, AT1 and AT2) was evaluated using western blot and immunofluorescence. Platelets were incubated in vitro with either Captopril or different RAS peptides including Alamandine, Angiotensin-I, Angiotensin-II, Angiotensin-(1–7), and Angiotensin-(1–9). Platelet adhesion was measured by spectrophotometry using BCECF fluorescence. Platelet activation and aggregation were analyzed using aggregometry after stimulation with extracellular matrix proteins. ACE and ACE2 activity were assessed using Fluorescent Peptides (FPS). We demonstrated that healthy human platelets express all the tested RAS receptors. However, RAS peptides did not modulate platelet adhesion or aggregation despite a wide range of concentrations tested. ACE activity was detected in platelet lysates, but it was not inhibited by Captopril, while ACE2 activity was undetectable. Our findings suggest that while RAS receptors are expressed in platelets, RAS peptides do not impact platelet function, at least in our experimental setting. COVID-19 coagulopathy may occur independently of the RAS.
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spelling doaj-art-a6108d8d3f944e649c1bf851d2fce8762025-08-20T04:03:17ZengTaylor & Francis GroupPlatelets0953-71041369-16352025-12-0136110.1080/09537104.2025.2546982The renin-angiotensin system in healthy human platelets: expressed but inactiveFrançois Panosetti0François M. Cuenot1Damian S. Saint Auguste2Ana C. Martins Cavaco3Allancer D. C. Nunes4Philip H. J. Lu5Céline Magrini6Max Molot7Gabriel Sanglard8Rodi Günçü9Yassine Zouaghi10Charles Béguelin11Augusto Martins Lima12Nikolaos Stergiopulos13Laboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandFaculdade de Medicina e ciéncas biomédicas, Universidade do Algarve, Faro, PortugalInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USALaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandNational Institute of Science and Technology in Nanobiopharmaceutics (INCT-Nanobiofar), Instituto de Ciências Biológicas Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandFaculty of Medicine, University of Bern, Bern, SwitzerlandLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandLaboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandPlatelets play a crucial role in arterial thrombus formation, offering potential for new antiplatelet therapies with reduced bleeding risk. Here, we investigated the role of the renin-angiotensin system (RAS) in human platelets and explored its potential link to COVID-19 coagulopathy. Experiments were performed ex vivo on healthy human platelets. The expression of RAS receptors (Mas, MrgD, ACE, ACE2, AT1 and AT2) was evaluated using western blot and immunofluorescence. Platelets were incubated in vitro with either Captopril or different RAS peptides including Alamandine, Angiotensin-I, Angiotensin-II, Angiotensin-(1–7), and Angiotensin-(1–9). Platelet adhesion was measured by spectrophotometry using BCECF fluorescence. Platelet activation and aggregation were analyzed using aggregometry after stimulation with extracellular matrix proteins. ACE and ACE2 activity were assessed using Fluorescent Peptides (FPS). We demonstrated that healthy human platelets express all the tested RAS receptors. However, RAS peptides did not modulate platelet adhesion or aggregation despite a wide range of concentrations tested. ACE activity was detected in platelet lysates, but it was not inhibited by Captopril, while ACE2 activity was undetectable. Our findings suggest that while RAS receptors are expressed in platelets, RAS peptides do not impact platelet function, at least in our experimental setting. COVID-19 coagulopathy may occur independently of the RAS.https://www.tandfonline.com/doi/10.1080/09537104.2025.2546982ACE2adhesionaggregationCOVID-19human plateletrenin-angiotensin system
spellingShingle François Panosetti
François M. Cuenot
Damian S. Saint Auguste
Ana C. Martins Cavaco
Allancer D. C. Nunes
Philip H. J. Lu
Céline Magrini
Max Molot
Gabriel Sanglard
Rodi Günçü
Yassine Zouaghi
Charles Béguelin
Augusto Martins Lima
Nikolaos Stergiopulos
The renin-angiotensin system in healthy human platelets: expressed but inactive
Platelets
ACE2
adhesion
aggregation
COVID-19
human platelet
renin-angiotensin system
title The renin-angiotensin system in healthy human platelets: expressed but inactive
title_full The renin-angiotensin system in healthy human platelets: expressed but inactive
title_fullStr The renin-angiotensin system in healthy human platelets: expressed but inactive
title_full_unstemmed The renin-angiotensin system in healthy human platelets: expressed but inactive
title_short The renin-angiotensin system in healthy human platelets: expressed but inactive
title_sort renin angiotensin system in healthy human platelets expressed but inactive
topic ACE2
adhesion
aggregation
COVID-19
human platelet
renin-angiotensin system
url https://www.tandfonline.com/doi/10.1080/09537104.2025.2546982
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