Although human platelets express all major renin-angiotensin system receptors, angiotensin peptides did not influence platelet adhesion or aggregation, suggesting COVID-19 coagulopathy may not be driven by RAS-platelet interactions.
Expressed but inactiveAll six RAS receptors present on platelets, but no angiotensin peptide affected platelet function at any concentration
What the researchers found
Healthy human platelets express RAS receptors (Mas, MrgD, ACE, ACE2, AT1, AT2) but angiotensin peptides (Ang-I, Ang-II, Ang-(1-7), Ang-(1-9), alamandine) had no effect on platelet adhesion or aggregation at any concentration tested. ACE activity was present but captopril-resistant; ACE2 was undetectable.
Why it matters
This negative finding is important because it helps rule out direct RAS-platelet interactions as a mechanism for COVID-19 coagulopathy, redirecting research toward other pathways. It also clarifies the functional status of RAS components in platelets.
The numbers in context
Tested Captopril, Alamandine, Angiotensin-I, Angiotensin-II, Angiotensin-(1-7), and Angiotensin-(1-9) across a wide range of concentrations. Measured adhesion by BCECF fluorescence and aggregation by aggregometry.
How the study worked
Ex vivo study on healthy human platelets using western blot and immunofluorescence for receptor expression, spectrophotometry for adhesion, aggregometry for activation/aggregation, and fluorescent peptide substrates for enzyme activity.
Who was studied
Healthy human platelet samples (ex vivo)
What this study cannot tell us
Study used only healthy donor platelets—results may differ in disease states (COVID-19, hypertension) where RAS is dysregulated. Ex vivo conditions may not fully replicate in vivo platelet behavior. The captopril-resistant ACE activity suggests a non-canonical form that warrants further investigation.
How to read the evidence
Well-designed ex vivo human platelet study with multiple validated assays. Negative result is well-supported by comprehensive testing across peptides and concentrations, though limited to healthy donors.
When this study was published
Published in 2025; addresses the ongoing question of RAS involvement in COVID-19 coagulopathy.
The bigger picture
The renin-angiotensin system has been extensively studied in the context of COVID-19 due to the virus using ACE2 for cell entry. This study helps clarify that while platelets express the molecular machinery of RAS, the system appears functionally inactive in healthy platelets, narrowing the search for mechanisms behind COVID-related clotting disorders.
Questions still open
- Could RAS-platelet interactions become functionally relevant in disease states like COVID-19 or hypertension?
- What is the captopril-resistant ACE-like activity detected in platelet lysates?
- If RAS does not drive COVID-19 coagulopathy through platelets, what alternative pathways are responsible?
Common questions
What is the renin-angiotensin system and why was it studied in platelets?
Why is this negative result significant?
Read the original research
The renin-angiotensin system in healthy human platelets: expressed but inactive.
Platelets, 36(1), 2546982
Citation
Panosetti, François; Cuenot, François M; Saint Auguste, Damian S; Martins Cavaco, Ana C; Nunes, Allancer D C; Lu, Philip H J; Magrini, Céline; Molot, Max; Sanglard, Gabriel; Günçü, Rodi; Zouaghi, Yassine; Béguelin, Charles; Martins Lima, Augusto; Stergiopulos, Nikolaos. (2025). The renin-angiotensin system in healthy human platelets: expressed but inactive.. Platelets, 36(1), 2546982. https://doi.org/10.1080/09537104.2025.2546982