Project description
Mechanical cues guiding angiogenesis after heart attack
Most tissues have an inherent capacity to regenerate, maintaining homeostasis and function. In acute myocardial infarction (AMI), heart tissue is deprived of oxygen and nutrients, leading to cell death. Current therapies are designed to contain cellular damage but fail to regenerate vessels that can sustain the development of new cells. The ERC-funded PRIMA project aims to address insufficient angiogenesis after AMI by investigating the role of mechanical cues in the injured heart. The research team will utilise in vitro systems that mimic cardiac tissue and computational models to decode how mechanical memory influences vessel growth. The work will identify mechanoresponsive pathways as therapeutic targets, opening strategies to revascularise the heart and transform regenerative cardiology.
Objective
Acute myocardial infarction (AMI) is a significant global health issue. Current therapies cannot regenerate the hearts of survivors, leading to frequent AMI recurrence and premature death. Crucially, these therapies fail to induce sufficient blood vessel formation, i.e. angiogenesis, which is essential to regenerate the cardiac microvasculature. Without this vasculature, cells repopulating the infarcted tissue cannot survive. A deeper understanding and better control of post-AMI angiogenesis would thus transform patient outcomes.
Cells in the infarcted heart experience complex, time-evolving mechanical environments. Despite the proven role of mechanical stimuli in regulating angiogenesis in other tissues, the impact of evolving cardiac mechanical cues on post-AMI angiogenesis is unclear. With PRIMA, I aim to mechanistically understand how these evolving cues affect post-AMI angiogenesis and how to leverage this new understanding to regenerate the microvasculature.
I will achieve this aim by developing a revolutionary framework featuring in vitro and in silico models of cardiac angiogenesis. These models will address the evolving mechanical cues of the infarcted heart and the cell memory of past mechanical cues (mechanical memory). The new in vitro models will expose cells to mechanical cues mimicking the cardiac tissue. The resulting insights will inform multiscale computational models to predict angiogenesis and its subcellular mechanisms in response to macroscale changes in cardiac mechanical cues. The multiscale simulations, validated by in vitro models, will finally translate the in vitro findings to the complex in vivo setting and will identify new strategies to restore the microvasculature post-AMI.
Building on this unique idea and multidisciplinary approach, PRIMA will have a ground-breaking impact on cardiac interventions, by revealing mechanical cues and cell mechanoresponsive mechanisms as new targets to maximize cardiac revascularization and function.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology tissue engineering
- medical and health sciences clinical medicine cardiology cardiovascular diseases
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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(opens in new window) ERC-2025-STG
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5612 AE Eindhoven
Netherlands
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