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The Role of Adipose-Tissue Derived wnt-ligands in the Regulation of Myocardial Redox Signalling

Periodic Reporting for period 1 - REDOxHEART (The Role of Adipose-Tissue Derived wnt-ligands in the Regulation of Myocardial Redox Signalling)

Reporting period: 2015-07-01 to 2017-06-30

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.
Since its begging, the REDOxHEART project has managed to recruit 140 patients through the Oxford CABG Bio-resource biobank. We have collected their right atrium appendages (RAA), which is a small part of the small chamber of the heart, and have already measured ROS production from several sources. We have also completed clinical data and several wnt ligand gene expression. We are planning to perform further studies to evaluate the association between the level of ROS production, wnt ligands and patients’ outcomes. In addition, we have used an established heart cell model in order to perform experiments that enhanced our understanding on how some substances are activated by the wnt ligands and ultimately lead to increased ROS production.
The REDOxHEART project is aiming to inform the public about cardiovascular disease and about the research that is conducted at University of Oxford. To this purpose we have launched a website available to the public, which is also part of the Oxford CABG Bio-resource biobank website. This website is regularly updated in order to inform the public about the progress of our research and any major breakthroughs during the study. Furthermore, we have been participating in several public open day events, taking questions from the public and explaining the importance of research in the field of cardiovascular medicine. The REDOxHEART project and its findings so far have been presented to scientific meetings and events as well as within the University of Oxford’s seminars. The overall aim is to increase the scientific impact of the project and potentially form a new collaborations with other scientists from different departments.