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Understanding the role of macrophages in the structural degeneration of bioprosthetic heart valve leaflets

Project description

Characterisation of immune responses against heart valve prostheses

Valve replacement is frequently performed in patients suffering from valvular heart disease. Mechanical valve prostheses are durable but have a risk of thrombosis. On the other hand, valve replacements made of biocompatible tissue often degenerate and require reintervention. The EU-funded MACROVALVE project aims to address the cause of this degradation and investigate the role of macrophages. Using multi-omics technologies and electron microscopy, researchers will characterise the structural changes of bioprosthetic replacement valves in response to different biological and mechanical stimuli. Project results will shed light on the immune responses against such prostheses and fuel future efforts to improve their longevity and function.

Objective

Heart valve disease is predicted to be the next cardiac epidemic. Valve prostheses used to treat this disease are comprised of biological tissue. However, these bioprosthetic leaflets degrade, limiting their long-term efficacy. Macrophages have been found within explanted leaflets and are key determinants of biocompatible outcome. However, their role in bioprosthetic leaflet remodelling is poorly understood. Males and females for unknown reasons are also predisposed to calcific and fibrotic leaflet degeneration, respectively. MACROVALVEs goal is to elucidate the contribution of macrophages to the fibro-calcific remodelling of bioprosthetic leaflets. First, the applicant will apply histological, multi-omics and network analyses to constitute an integrated multi-omics map of human bioprosthetic leaflet degeneration. The differential pathogenesis between male and female disease will be determined. The results will also be compared against data for native aortic valve disease at different stages: early-disease, fibrotic and calcified. Electron microscopy will be used to identify extracellular vesicles. Secondly, the discrete response of sex-separated macrophages in the presence of hormonal milieu and physiological stimulation will be investigated. Ultimately, the innovative application of these techniques to unravel the innate immune response to bioprosthetic replacements will pave the way for novel therapeutics to prolong leaflet lifespan. The project is in line with the Horizon 2020 focus area Health, Demographic Change and Wellbeing. The candidate will spend the first two years of this fellowship training in multi-omics and network analyses at Brigham and Womens Hospital in the United States. She will transfer these skills to Ireland during the return phase and increase Europes reputation as a location of cutting-edge research. Through this fellowship, the applicant will reach a position of professional maturity required for success in her future career.

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

UNIVERSITY OF GALWAY
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.

€ 257 561,28
Address
UNIVERSITY ROAD
H91 Galway
Ireland

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Region
Ireland Northern and Western West
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.

€ 257 561,28

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