The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study
Pasquale Pignatelli,
Francesco Baratta,
Raffaella Buzzetti,
Alessandra D’Amico,
Valentina Castellani,
Simona Bartimoccia,
Antonio Siena,
Luca D’Onofrio,
Ernesto Maddaloni,
Annachiara Pingitore,
Giovanni Alfonso Chiariello,
Francesca Santilli,
Daniele Pastori,
Nicholas Cocomello,
Francesco Violi,
Maria Del Ben,
Vittoria Cammisotto,
Roberto Carnevale
Affiliations
Pasquale Pignatelli
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Francesco Baratta
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Raffaella Buzzetti
Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
Alessandra D’Amico
Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, Italy
Valentina Castellani
Department of General Surgery and Surgical Specialty Paride Stefanini, Sapienza University of Rome, 00161 Rome, Italy
Simona Bartimoccia
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Antonio Siena
Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
Luca D’Onofrio
Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
Ernesto Maddaloni
Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
Annachiara Pingitore
Department of General Surgery and Surgical Specialty Paride Stefanini, Sapienza University of Rome, 00161 Rome, Italy
Giovanni Alfonso Chiariello
Cardiovascular Sciences Department, Agostino Gemelli Foundation Polyclinic IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy
Francesca Santilli
Department of Medicine and Aging, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University Foundation, 66100 Chieti, Italy
Daniele Pastori
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Nicholas Cocomello
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Francesco Violi
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Maria Del Ben
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Vittoria Cammisotto
Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Sodium–glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activation and thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing metformin therapy. The population was divided into two groups: treatment with GLP-1 receptor agonists (GLP-1RA, Group A) and gliflozins (Group B). Oxidative stress, platelet activation and thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline, gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p 2O2 production (−53.4%, p p p p p p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with gliflozins (10–30 μM) showed a reduction in oxidative stress, platelet activation and thrombus growth. Our results showed that gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection.
