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

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/656990
Start date: 01-07-2015
End date: 30-06-2017
Total budget - Public funding: 183 454,80 Euro - 183 454,00 Euro
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Original description

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.

Status

CLOSED

Call topic

MSCA-IF-2014-EF

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2014
MSCA-IF-2014-EF Marie Skłodowska-Curie Individual Fellowships (IF-EF)