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

Informazioni relative al progetto

POSTA

ID dell’accordo di sovvenzione: 101025074

DOI

10.3030/101025074

Progetto concluso il 31 Luglio 2022

Data della firma CE 23 Marzo 2021

Data di avvio 1 Agosto 2021

Data di completamento 31 Luglio 2023

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 162 806,40

Contributo UE

€ 162 806,40

Coordinato da

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.)

Periodo di rendicontazione: 2021-08-01 al 2023-07-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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)

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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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