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. MACROVALVE’s 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 Women’s Hospital in the United States. She will transfer these skills to Ireland during the return phase and increase Europe’s 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.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
H91 Galway
Ireland