Potential Role of Mitochondria as Modulators of Blood Platelet Activation and Reactivity in Diabetes and Effect of Metformin on Blood Platelet Bioenergetics and Platelet Activation.

Karolina Siewiera, Magdalena Labieniec-Watala, Hassan Kassassir, Nina Wolska, Dawid Polak, Cezary Watala

International journal of molecular sciences 2022 Mar 27

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Blood platelet dysfunctions are strongly involved in the development of the micro- and macrovascular complications in diabetes mellitus (DM). However, the molecular causes of abnormal platelet activation in DM remain unclear. Experimental data suggests that platelet mitochondria can regulate the prothrombotic phenotype of platelets, and changes in these organelles may influence platelet activation and modify platelet responses to stimulation. The present study evaluates the impact of DM on mitochondrial respiratory parameters and blood platelet activation/reactivity in a rat model of experimental diabetes following 1, 2.5 and 5 months of streptozotocin (STZ)-induced diabetes. Moreover, a mild inhibition of the mitochondrial respiratory chain with the use of metformin under in vitro and in vivo conditions was tested as a method to reduce platelet activation and reactivity. The platelets were studied with a combination of flow cytometry and advanced respirometry. Our results indicate that prolonged exposure of blood platelets to high concentrations of glucose, as in diabetes, can result in elevated blood platelet mitochondrial respiration; this may be an effect of cell adaptation to the high availability of energy substrates. However, as these alterations occur later than the changes in platelet activation/reactivity, they may not constitute the major reason for abnormal platelet functioning in DM. Moreover, metformin was not able to inhibit platelet activation and reactivity under in vitro conditions despite causing a decrease in mitochondrial respiration. This indicates that the beneficial effect of metformin on the coagulation system observed in vivo can be related to other mechanisms than via the inhibition of platelet activation.

Citation

Karolina Siewiera, Magdalena Labieniec-Watala, Hassan Kassassir, Nina Wolska, Dawid Polak, Cezary Watala. Potential Role of Mitochondria as Modulators of Blood Platelet Activation and Reactivity in Diabetes and Effect of Metformin on Blood Platelet Bioenergetics and Platelet Activation. International journal of molecular sciences. 2022 Mar 27;23(7)