The Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study.
Pasquale PignatelliFrancesco BarattaRaffaella BuzzettiAlessandra D'AmicoValentina CastellaniSimona BartimocciaAntonio SienaLuca D'OnofrioErnesto MaddaloniAnnachiara PingitoreGiovanni Alfonso ChiarielloFrancesca SantilliDaniele PastoriNicholas CocomelloFrancesco VioliMaria Del BenVittoria CammisottoRoberto CarnevalePublished in: Antioxidants (Basel, Switzerland) (2022)
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 < 0.001), H 2 O 2 production (-53.4%, p < 0.001), TxB2 (-33.1%, p < 0.001), sP-selectin (-49.3%, p < 0.001) and sCD40L levels (-62.3%, p < 0.001) as well as thrombus formation (-32%, p < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, 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.
Keyphrases
- oxidative stress
- dna damage
- ischemia reperfusion injury
- diabetic rats
- induced apoptosis
- open label
- newly diagnosed
- randomized controlled trial
- ejection fraction
- combination therapy
- clinical trial
- end stage renal disease
- mesenchymal stem cells
- risk factors
- prognostic factors
- radiation therapy
- study protocol
- idiopathic pulmonary fibrosis
- peritoneal dialysis
- reactive oxygen species
- red blood cell
- endoplasmic reticulum stress
- anti inflammatory