MACROVALVE · Understanding the role of macrophages in the structural degeneration of bioprosthetic heart valve leaflets
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-09-01 → 2025-08-31
- EU contribution
- €257,561
- Participants
- 2
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Understanding the role of macrophages in the structural degeneration of bioprosthetic heart valve leaflets
The prevalence of aortic valve (AV) stenosis in individuals aged 75 years or older is 12.4%, and the incidence increases with age. Accordingly, the number of patients requiring valve replacement annually is expected to rise to over 850,000 globally by 2050. Currently, the only treatment option for heart valve disease is valve replacement. Valves can be sutured into place during open-heart surgery (surgical) or crimped onto a catheter and delivered percutaneously (transcatheter). Structural valve degeneration (SVD) is the inevitable and irreversible remodelling of a bioprosthetic valve, which limits the device lifespan. Up to one-third of patients exhibit subclinical SVD after only 8 years. Additionally, specific devices and patient populations are at risk of accelerated SVD. However, the mechanisms underlying SVD are still not fully understood. The overall goal of the fellowship is to uncover processes underlying bioprosthetic (BP) heart valve degeneration. This goal is broken down into two objectives: 1) to examine the regulatory molecular networks and 2) to elucidate the role of host inflammatory macrophages. Mass spectrometry has become the leading modality for analysing complex protein samples. Therefore, objective 1 set out to conduct a histopathological assessment of BP degeneration and build proteomic comparison maps of BP degeneration versus native AV disease. Within this cohort, subanalyses will be conducted where possible to determine the effect of patient factors such as sex, age, and length of implantation on subsequent bioprosthetic degeneration. Secondly, the immune response is a critical determinant of implant longevity. Therefore, the second objective proposes to investigate the contribution of host macrophages to leaflet degeneration under biomechanical loading.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- UNIVERSITY OF GALWAY · GalwayCoordinatorIreland
- BRIGHAM INC · BostonUnited States
Links
Data: CORDIS, © European Union