The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study
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 gliflozi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/10/1878 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Pasquale Pignatelli |
| collection | DOAJ |
| description | 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%, <i>p</i> < 0.001), H<sub>2</sub>O<sub>2</sub> production (−53.4%, <i>p</i> < 0.001), TxB2 (−33.1%, <i>p</i> < 0.001), sP-selectin (−49.3%, <i>p</i> < 0.001) and sCD40L levels (−62.3%, <i>p</i> < 0.001) as well as thrombus formation (−32%, <i>p</i> < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, <i>p</i> < 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. |
| first_indexed | 2024-03-09T20:49:38Z |
| format | Article |
| id | doaj.art-76d4c14f0fb246c9952d6594bc5898e4 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T20:49:38Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-76d4c14f0fb246c9952d6594bc5898e42023-11-23T22:37:13ZengMDPI AGAntioxidants2076-39212022-09-011110187810.3390/antiox11101878The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot StudyPasquale Pignatelli0Francesco Baratta1Raffaella Buzzetti2Alessandra D’Amico3Valentina Castellani4Simona Bartimoccia5Antonio Siena6Luca D’Onofrio7Ernesto Maddaloni8Annachiara Pingitore9Giovanni Alfonso Chiariello10Francesca Santilli11Daniele Pastori12Nicholas Cocomello13Francesco Violi14Maria Del Ben15Vittoria Cammisotto16Roberto Carnevale17Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyDepartment of General Surgery and Surgical Specialty Paride Stefanini, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of General Surgery and Surgical Specialty Paride Stefanini, Sapienza University of Rome, 00161 Rome, ItalyCardiovascular Sciences Department, Agostino Gemelli Foundation Polyclinic IRCCS, Catholic University of the Sacred Heart, 00168 Rome, ItalyDepartment of Medicine and Aging, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University Foundation, 66100 Chieti, ItalyDepartment of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, ItalyMediterranea Cardiocentro, 80122 Napoli, ItalySodium–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%, <i>p</i> < 0.001), H<sub>2</sub>O<sub>2</sub> production (−53.4%, <i>p</i> < 0.001), TxB2 (−33.1%, <i>p</i> < 0.001), sP-selectin (−49.3%, <i>p</i> < 0.001) and sCD40L levels (−62.3%, <i>p</i> < 0.001) as well as thrombus formation (−32%, <i>p</i> < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, <i>p</i> < 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.https://www.mdpi.com/2076-3921/11/10/1878gliflozinstype 2 diabetesoxidative stressplatelet activationthrombosis |
| spellingShingle | 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 The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study Antioxidants gliflozins type 2 diabetes oxidative stress platelet activation thrombosis |
| title | The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study |
| title_full | The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study |
| title_fullStr | The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study |
| title_full_unstemmed | The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study |
| title_short | The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study |
| title_sort | sodium glucose co transporter 2 sglt2 inhibitors reduce platelet activation and thrombus formation by lowering nox2 related oxidative stress a pilot study |
| topic | gliflozins type 2 diabetes oxidative stress platelet activation thrombosis |
| url | https://www.mdpi.com/2076-3921/11/10/1878 |
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