Novel insights into sex-specific and oestrogen-dependent mechanisms in myocardial ischaemia/reperfusion injury

Informazioni relative al progetto

SEXOGENIRI

ID dell’accordo di sovvenzione: 101024324

DOI

10.3030/101024324

Progetto concluso il 28 Gennaio 2022

Data della firma CE 19 Marzo 2021

Data di avvio 1 Giugno 2021

Data di completamento 31 Maggio 2024

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 294 359,04

Contributo UE

€ 294 359,04

Coordinato da

HASKOLI ISLANDS
Iceland

Periodic Reporting for period 1 - SEXOGENIRI (Novel insights into sex-specific and oestrogen-dependent mechanisms in myocardial ischaemia/reperfusion injury)

Periodo di rendicontazione: 2021-06-01 al 2024-05-31

Sintesi del contesto e degli obiettivi generali del progetto

Acute myocardial infarction (MI) accounts for millions of morbidity and mortality cases worldwide. While the underlying pathophysiology of cardiomyocyte dysfunction and death during MI-related ischaemia/reperfusion injury (IRI), which occurs due to the restoration of coronary blood flow after MI, is well established, the relevance of sex-based differences in this context is poorly understood. In this action, we aim at understanding the effect of biological sex in the induction of a novel form of cell death in the setting of IRI.

The overall aim of the proposed research is to study the role of biological sex in oxeiptosis during myocardial IRI. The main hypothesis is that there is a sex-based difference in the occurrence of oxeiptosis following IRI. It is further hypothesised that E2 plays a major role in this process, potentially involving the modulation of the components of mitochondrial fusion (Fig. 1). The specific aims are to:
1) assess and characterise oxeiptosis in male vs. female mice following IRI;
2) investigate the potential role of E2 in the induction of oxeiptosis in IRI;
3) assess the regulation of mitochondrial fusion proteins by E2 in oxeiptosis following IRI;
4) identify potential small-molecule candidates that can inhibit the occurrence of H2O2-induced oxeiptosis and preserve mitochondrial morphology and function;
5) assess the levels of selected candidates involved in oxeiptosis and mitochondrial fusion proteins in LV samples from adult male and female patients with ischaemic cardiomyopathy, thereby taking a translational approach.

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

As the project was terminated early, i.e. within the first six months, no major work could be completed towards any of the objectives of the project.

As part of the dissemination and communication strategy, the research fellow and the supervisor authored and published the following review article in an open access journal:

Beikoghli Kalkhoran S, Kararigas G. Oestrogenic Regulation of Mitochondrial Dynamics. Int J Mol Sci 2022;23(3):1118

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)

Not applicable due to early termination of the project.