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Article Dans Une Revue Journal of Diabetes & Metabolism Année : 2020

Large triglyceride-rich lipoproteins from fasting patients with type 2 diabetes activate platelets

Résumé

Aims: Type 2 diabetes (T2D) patients present with risk factors for atherothrombosis such as fasting hypertriglyceridaemia and platelet hyperactivity. Our study objective was to determine the effect of large triglyceride-rich lipoproteins (TGRL) from fasting T2D patients on platelet aggregation and, if any, to identify the signaling pathway involved. Methods: Large TGRL were isolated from the plasma of 25 T2D patients by ultracentrifugation (density < 1.000 g/mL). Platelets were isolated from healthy blood donors (HBD) and suspended in buffer, then preincubated in the presence or absence of TGRL and stimulated with either collagen or thrombin. Platelet aggregation and the arachidonic acid (AA) signaling pathway were studied. Results: Fasting T2D large TGRL were mostly of hepatic origin (apoB100/apoB48 ratio: 42 ± 7) and rich in triglycerides (TG/total apoB ratio: 4.2 ± 0.5), and able to potentiate agonist-stimulated platelet aggregation (collagen: +68%, P < 0.05; thrombin: +771%, P < 0.05). It should also be mentioned that TGRL from the plasma of HBD (n = 7) had no effect on platelet aggregation. In addition, T2D large TGRL increased thromboxane B2 (TxB2) concentration in platelets stimulated with either collagen (+34%, P < 0.05) or thrombin (+37%, P < 0.05) compared with platelets stimulated with either of these agonists without TGRL. Phosphorylation of p38 MAPK and cytosolic phospholipase A2 (cPLA2) was enhanced after incubation of platelets with T2D TGRL and thrombin (+87% and +32%, respectively, P < 0.05) compared with platelets incubated with thrombin only. Conclusion: Large TGRL from fasting T2D patients may play a role in the development of atherothrombosis by increasing platelet aggregation and activating the platelet AA signaling pathway
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Dates et versions

hal-02996611 , version 1 (09-11-2020)

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Marie Michèle Boulet, D. Cheillan, M. Di Filippo, C. Buisson, Marie-Caroline Michalski, et al.. Large triglyceride-rich lipoproteins from fasting patients with type 2 diabetes activate platelets. Journal of Diabetes & Metabolism, 2020, 46 (1), pp.54-60. ⟨10.1016/j.diabet.2019.03.002⟩. ⟨hal-02996611⟩
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