Oxidative stress and platelet hyperactivity: the role of NADPH oxidases in haemostasis regulation in health and diabetes.

Información del proyecto

POSTA

Identificador del acuerdo de subvención: 101025074

DOI

10.3030/101025074

Proyecto finalizado el 31 Julio 2022

Fecha de la firma de la CE 23 Marzo 2021

Fecha de inicio 1 Agosto 2021

Fecha de finalización 31 Julio 2023

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 162 806,40

Aportación de la UE

€ 162 806,40

Coordinado por

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF
Germany

Periodic Reporting for period 1 - POSTA (Oxidative stress and platelet hyperactivity: the role of NADPH oxidases in haemostasis regulation in health and diabetes.)

Período documentado: 2021-08-01 hasta 2023-07-31

Resumen del contexto y de los objetivos generales del proyecto

Currently, 70% of T2DM patients succumb to cardiovascular diseases. I have been working on pro-oxidant enzymes called NADPH oxidases (NOXs), which are responsible for oxidative stress and activation of platelets. We have shown that the enzymatic activity of NOXs generates oxidant molecules in conditions modelling diabetes (i.e. hyperglycaemia), which in turn drives platelet hyperactivity and increases the risk of thrombosis. This is an important novel information regarding the links between diabetes and cardiovascular disease. Targeting NOX-generated oxidant molecules may become a valuable strategy to protect diabetes patients from cardiovascular diseases. Considering the prevalence of diabetes in European countries, this project may have a substantial impact on society by reducing diabetes-dependent morbidity and associated healthcare costs.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

The objective of WP1 was to understand how NOX1 regulate platelets. As detailed in the work description, we used a variety of techniques and improved significantly our understanding of the processes in which NOX1 is involved. The results are being organised in a manuscript that we intend to submit for publication early in 2023. The proteomics work described in WP2 has been performed and data analysis in undergoing. This includes the volcano plot submitted as representative figure from the work so far. The results from WP2 will be submitted for publication as 2 manuscripts in early 2023. These data highlighted the activation of cell stress responses and shed new light on the mechanism making platelet hyperactive in diabetes.
Overall, the work from this project will be incorporated in 2 manuscripts that will be submitted to: 1) Journal of Thrombosis and Haemostasis. 2) Journal of Proteomics.
In the meanwhile, I have acknowledged financial support from ERC in two manuscripts on studies related but not included in this project.
1. Tarafdar A, Wolska N, Krisp C, Schlüter H, Pula G (2022) The amyloid peptide β disrupts intercellular junctions and increases endothelial permeability in a NADPH oxidase 1-dependent manner. Redox Biology [ahead of printing]. (IF 11.8)
2. Wallis S, Wolska N, Englert H, Posner M, Upadhyay A, Renné T, Eggleston I, Bagby S, Pula G. (2022) A peptide from the staphylococcal protein Efb binds P-selectin and inhibits the interaction of platelets with leukocytes. J Thromb Haemost. 20(3):729-741. (IF 16.0)

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

The manuscripts that we will publish to present the results from this project will be an incremental but substantial advance on our understanding of cardiovascular disease in diabetes. Any improvement on the current understanding of such a widespread health problem will have relevant societal impact.

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