REDOxHEART · The Role of Adipose-Tissue Derived wnt-ligands in the Regulation of Myocardial Redox Signalling
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-07-01 → 2017-06-30
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
The Role of Adipose-Tissue Derived wnt-ligands in the Regulation of Myocardial Redox Signalling
Cardiovascular disease (CVD) is the leading cause or morbidity and mortality in the developed world and particularly across the European population. CVD can manifest as a heart attack or stroke depending on the area of the body that has been affected. Reactive oxygen species (ROS) are highly reactive molecules that are produced in our body from several enzymes and under normal circumstances play a key role in cell communication and defence from several pathogens. The equilibrium of the ROS producing systems and the antioxidant ones is widely known as redox state. If that equilibrium is disrupted towards the production of more ROS we have a condition called oxidative stress. Oxidative stress is now known to be one of the major factors for the progression of CVD Obesity is also well known that it contributes to Recently it has also been proposed that the adipose tissue (fat) around the heart might also play a key role in regulating redox state. The aim of this project is to identify novel mechanisms and molecules that are produced from the adipose tissue or the heart and contribute towards the development and progression heart related diseases (hypertrophy, atrial fibrillation). Understanding the basic mechanisms of CVD can help identify novel therapeutic targets and potential biomarkers of CVD, thus helping identify earlier and potentially reducing cardiovascular events. The socioeconomic impact of this study is expected to be very high due to the number of individuals affected each year in Europe.
Data: CORDIS, © European Union
Project objective
Myocardial redox signalling is a critical regulator of myocardial physiology and a therapeutic target in cardiovascular science, while obesity seems to trigger myocardial oxidative stress. The non-canonical wnt signalling pathways (Ca2+-dependent (CDP) and planar cell polarity pathway (PCP)) are important in cardiac development and they are also involved in obesity (wnt ligands are involved in adipose tissue expansion), although their role in the adult myocardium is unknown. We propose to define the role of CDP and PCP in the regulation of myocardial redox state in the human adult heart. We will perform a) Clinical association studies using tissue from patients undergoing cardiac surgery to test for paracrine effects of adipose tissue on myocardial PCP/CDP regulation b) Studies using ex vivo models of human myocardium (trabeculae) to test the role of CDP/PCP in myocardial redox state regulation c) Cell culture studies using primary human cardiomyocytes to explore the mechanisms of these effects d) Animal studies using a novel transgenic mouse model to test causality of the associations. In this translational study we will explore for the first time the role of CDP/PCP in the regulation of myocardial redox signalling and evaluate its role in cardiac physiology. This work may identify novel disease biomarkers and therapeutic targets for the treatment of myocardial diseases.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union