Involvement of hyperglycemia in the development of platelet procoagulant response: the role of aldose reductase and platelet swelling
| Autor: | Tomasz Rusak, Marian Tomasiak, Tomasz Misztal, Malgorzata Rusak, Justyna Brańska-Januszewska |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Blood Platelets Male medicine.medical_specialty Adolescent Platelet Aggregation 030204 cardiovascular system & hematology Platelet reactivity 03 medical and health sciences Young Adult 0302 clinical medicine Aldehyde Reductase Internal medicine Diabetes mellitus medicine Diabetes Mellitus Humans Sorbitol Platelet Platelet activation Mean platelet volume Blood Coagulation Cell Size Aldose reductase business.industry Thrombin Hematology General Medicine medicine.disease Platelet Activation 030104 developmental biology Increased risk Endocrinology Hyperglycemia Female business Thrombotic complication |
| Zdroj: | Blood coagulationfibrinolysis : an international journal in haemostasis and thrombosis. 28(6) |
| ISSN: | 1473-5733 |
| Popis: | Rise in mean platelet volume (MPV) has been demonstrated to be associated with increased platelet reactivity. In diabetes patients, augmented MPV was proposed to contribute to increased risk of thrombotic complications. Therefore, the aim of this study was to investigate whether under hyperglycemic conditions, aldose reductase (AR)-mediated sorbitol formation and associated rise in cell volume, which subsequently results in platelet hyperactivation. Platelets were obtained from 30 healthy volunteers and 13 patients with diabetes. We evaluated changes in platelet size, their reactivity (measured as aggregation and secretion), and sorbitol content evoked by glucose. Measurement of procoagulant activity and thromboelastography were performed to assess how hyperglycemia affects coagulation. We have found that incubation of platelets with glucose (10 mmol/l) leads to increased MPV, potentiation of collagen-evoked platelet aggregation, secretion, and procoagulant response (measured as platelet-dependent thrombin generation and phosphatidylserine expression). Glucose-treated platelets had higher sorbitol content and demonstrated enhanced tubulin polymerization. All the above-mentioned phenomena were reduced following the blocking of AR or by vincristine (microtubule destabilizing agent). Thromboelastography measurements demonstrated that hyperglycemia is associated with reduction of clotting time (R) and increase in the alpha angle (reflects platelet activation). Addition of sorbinil (AR inhibitor) or vincristine normalized R variable and alpha angle. The hyperglycemic conditions may accelerate platelet-related thrombin generation through the activation of polyol pathway, enhanced tubulin polymerization and associated with it rise in platelet volume. |
| Databáze: | OpenAIRE |
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