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

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.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 183 454,80
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 183 454,80
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