The Sodium–Glucose Co-Transporter-2 (SGLT2) Inhibitors Reduce Platelet Activation and Thrombus Formation by Lowering NOX2-Related Oxidative Stress: A Pilot Study

Figures

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  Figure 1. (a) Serum soluble NOX2-derived peptide (sNOX2-dp), (b) serum H2O2, and (c) blood HBA before and 15 days after administration of GLP-1RA (n = 16) or gliflozins (n = 16). Data are expressed as mean ± SD. Intra-group significance: * p < 0.05; *** p < 0.0001; inter-group significance: # p < 0.05.

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  Figure 2. (a) Thromboxane B2 production, (b) soluble P-selectin levels and (c) soluble CD40 ligand before and 15 days after administration of GLP-1RA (n = 16) or gliflozins (n = 16). Data are expressed as mean ± SD. Intra-group significance: * p < 0.05; ** p < 0.001; *** p < 0.0001; inter-group significance: # p < 0.05.

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  Figure 3. (a–c) In vivo effect of gliflozins therapy on platelet-dependent thrombus growth under laminar flow. Whole blood samples (T2D, n = 3) before treatment (PRE) and after 15 days of gliflozins therapy (POST). (d–f) In vitro effect of dapagliflozin (Dapa, 30 µM) on platelet-dependent thrombus growth under laminar flow in whole blood samples taken from HS (n = 3) and T2D patients (n = 3). Samples were analyzed by (a,d), area under the curve (AUC), and (b,e) occlusion time; (c,f), representative images of thrombus formation under laminar flow conditions. Data were expressed as mean ± SD; * p < 0.05, ** p < 0.01; ns = not significant.

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  Figure 4. (a) Platelet aggregation and representative aggregometer trace, (b) Thromboxane B2 production, (c) soluble P-selectin levels, (d) soluble CD 40 ligand, (e) serum soluble NOX2-derived peptide (sNOX2-dp), (f) serum H2O2 in washed platelets (wPLTs) taken from HS (n = 5) pre-incubated with or without d-Glucose (d-Glu, 10 mM) and then stimulated with or without STC of collagen (0.25 μg/mL) in the presence or less of dapagliflozin (Dapa, 30 µM) or dulaglutide (Dula, 100 nmol/L) or negative control (NC). Data were expressed as mean ± SD; * p < 0.05, ** p < 0.01; *** p < 0.001.