Cargando…

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

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 pro...

Descripción completa

Detalles Bibliográficos
Autores principales: Siewiera, Karolina, Labieniec-Watala, Magdalena, Kassassir, Hassan, Wolska, Nina, Polak, Dawid, Watala, Cezary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998700/
https://www.ncbi.nlm.nih.gov/pubmed/35409027
http://dx.doi.org/10.3390/ijms23073666
_version_ 1784685005990002688
author Siewiera, Karolina
Labieniec-Watala, Magdalena
Kassassir, Hassan
Wolska, Nina
Polak, Dawid
Watala, Cezary
author_facet Siewiera, Karolina
Labieniec-Watala, Magdalena
Kassassir, Hassan
Wolska, Nina
Polak, Dawid
Watala, Cezary
author_sort Siewiera, Karolina
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8998700
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89987002022-04-12 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 Siewiera, Karolina Labieniec-Watala, Magdalena Kassassir, Hassan Wolska, Nina Polak, Dawid Watala, Cezary Int J Mol Sci Article 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. MDPI 2022-03-27 /pmc/articles/PMC8998700/ /pubmed/35409027 http://dx.doi.org/10.3390/ijms23073666 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Siewiera, Karolina
Labieniec-Watala, Magdalena
Kassassir, Hassan
Wolska, Nina
Polak, Dawid
Watala, Cezary
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998700/
https://www.ncbi.nlm.nih.gov/pubmed/35409027
http://dx.doi.org/10.3390/ijms23073666
work_keys_str_mv AT siewierakarolina potentialroleofmitochondriaasmodulatorsofbloodplateletactivationandreactivityindiabetesandeffectofmetforminonbloodplateletbioenergeticsandplateletactivation
AT labieniecwatalamagdalena potentialroleofmitochondriaasmodulatorsofbloodplateletactivationandreactivityindiabetesandeffectofmetforminonbloodplateletbioenergeticsandplateletactivation
AT kassassirhassan potentialroleofmitochondriaasmodulatorsofbloodplateletactivationandreactivityindiabetesandeffectofmetforminonbloodplateletbioenergeticsandplateletactivation
AT wolskanina potentialroleofmitochondriaasmodulatorsofbloodplateletactivationandreactivityindiabetesandeffectofmetforminonbloodplateletbioenergeticsandplateletactivation
AT polakdawid potentialroleofmitochondriaasmodulatorsofbloodplateletactivationandreactivityindiabetesandeffectofmetforminonbloodplateletbioenergeticsandplateletactivation
AT watalacezary potentialroleofmitochondriaasmodulatorsofbloodplateletactivationandreactivityindiabetesandeffectofmetforminonbloodplateletbioenergeticsandplateletactivation