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
Laboratory of Hemodynamics and Cardiovascular Technology (LHTC), Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Faculty of Medicine, University of Bern, Bern, Switzerland.
Platelets. 2025 Dec;36(1):2546982. doi: 10.1080/09537104.2025.2546982. Epub 2025 Aug 18.
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 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 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.
血小板在动脉血栓形成中起关键作用，为降低出血风险的新型抗血小板治疗提供了潜力。在此，我们研究了肾素-血管紧张素系统（RAS）在人血小板中的作用，并探讨了其与COVID-19凝血病的潜在联系。对健康人血小板进行了实验。使用蛋白质印迹法和免疫荧光法评估RAS受体（Mas、MrgD、ACE、ACE2、AT1和AT2）的表达。将血小板与卡托普利或不同的RAS肽（包括阿拉曼丁、血管紧张素-I、血管紧张素-II、血管紧张素-(1-7)和血管紧张素-(1-9)）一起孵育。使用BCECF荧光通过分光光度法测量血小板粘附。在用细胞外基质蛋白刺激后，使用凝集法分析血小板活化和聚集。使用荧光肽（FPS）评估ACE和ACE2活性。我们证明健康人血小板表达所有测试的RAS受体。然而，尽管测试了广泛的浓度范围，RAS肽并未调节血小板粘附或聚集。在血小板裂解物中检测到ACE活性，但它不受卡托普利抑制，而未检测到ACE2活性。我们的研究结果表明，虽然RAS受体在血小板中表达，但RAS肽至少在我们的实验环境中不影响血小板功能。COVID-19凝血病可能独立于RAS发生。
