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- The renin-angiotensin system in healthy human platelets: expressed but inactivePublication . Panosetti, François; Cuenot, François M.; Auguste, Damian S. Saint; Martins Cavaco, Ana Cláudia; Nunes, Allancer D. C.; Lu, Philip H. J.; Magrini, Céline; Molot, Max; Sanglard, Gabriel; Günçü, Rodi; Zouaghi, Yassine; Béguelin, Charles; Lima, Augusto Martins; Stergiopulos, NikolaosPlatelets 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.
- A randomized controlled trial assessing the release of circulating tumor and mesenchymal cells in no-touch radical nephrectomyPublication . Leitão, Tito Palmela; Corredeira, Patrícia; Rodrigues, Carolina; Piairo, Paulina; Miranda, Miguel; Martins Cavaco, Ana Cláudia; Kucharczak, Sandra; Antunes, Marília; Peixoto, Sara; Reis, José Palma dos; Lopes, Tomé; Diéguez, Lorena; Costa, LuísAbstract: Background: Circulating tumor cells (CTCs) may be the missing renal cell carcinoma (RCC) biomarker. No-touch (NT) resection has shown benefit in several tumors. Methods: A randomized controlled trial comparing CTC and circulating mesenchymal cell (CMC) release in no-touch (NT) vs. conventional (C) laparoscopic RN. Blood samples were collected at operation room arrival (S0), specimen extraction (S1), postoperative D1, and D30. CTCs were isolated and analyzed using RUBYchip™. Results: Thirty-four patients were included. No significant differences were found between groups in CTC and CMC counts, count variations between time points, complications, and survival. The total circulating cell detection rates in the NT, C, and overall RCC groups were 58.3%, 80.0%, and 70.4% at S0; 41.6%, 86.7%, and 66.7% at S1; 50.0%, 64.3%, and 60.0% at D1; and 54.5%, 42.9%, and 44.0% at D30, respectively. A progressive decrease in CMCs was observed in the C group after surgery, especially at D1 (4.78 to 1.64 CMCs/7.5 mL blood, p = 0.035). Healthy controls had no circulating cells; however, high CMC counts were found in chronic inflammation controls and oncocytoma patients, with no significant difference from RCC patients (p = 0.460). Conclusions: NT RN did not reduce circulating cell release nor improve survival compared to C RN.