SEXOGENIRI · Novel insights into sex-specific and oestrogen-dependent mechanisms in myocardial ischaemia/reperfusion injury
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-06-01 → 2024-05-31
- EU contribution
- €294,359
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Novel insights into sex-specific and oestrogen-dependent mechanisms in myocardial ischaemia/reperfusion injury
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.
Data: CORDIS, © European Union
Project objective
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 project will examine both mouse and human hearts and will benefit from a range of techniques including, but not limited to in vivo surgery, in vitro cell line evaluation, state-of-the-art microscopy, mitochondrial respirometry and molecular biology methods. The content of the action will enable the researcher to restart his career and gain important academic, interpersonal and laboratory skills. It will also provide an opportunity for the researcher to publish in major journals and disseminate his findings to scientists and the public, which will ultimately help him establish himself in the field of cardiovascular science. The action also helps raise the research and academic profile of the host team and institution and contribute to the development of strong intra-European science networking. Overall, this action aims at contributing to the scientific progress of the researcher and pave the way for the identification of novel therapeutic targets for IRI with direct translational potential.
Original text from CORDIS.
Participants
- HASKOLI ISLANDS · ReykjavikCoordinatorIceland
Links
Data: CORDIS, © European Union