Introducing our Structure
EU-METAHEART has a solid background in the different sub-domains of Heart Failure research
The network includes: (i) basic researchers who are experts in cardiac metabolism, inflammation, mitochondria, EC coupling, redox biology and vascular disease; (ii) experts in omics-based tools; (iii) translational researchers who are experts in (small and large) animal models and state-of-the-art imaging modalities; and (iv) health care professionals.
Scientific methodologies
The Action will harness recent advances and breakthroughs in scientific methodologies, such as in:
- Omics-based technologies;
- In vitro technologies to assess mechano-energetic coupling in isolated cardiac myocytes;
- Small and large animal models for HFpEF and HFrEF, but also hereditary cardiomyopathies;
- In vivo functional, metabolic and immunological imaging;
- Well-characterized and –phenotyped cohorts of patients with HF and hereditary cardiomyopathies;
- Metabolically and functionally maturated human induced pluripotent stem cell (hiPSC)-derived cardiac myocytes from patients with hereditary cardiomyopathies.
Meet our Working Groups
We have identified four scientific key areas to which metabolic or mitochondrial dysfunction are central, which will be addressed by four Working Groups (WGs).
These research areas are tightly intertwined and can hardly be investigated separately. Therefore, EU-METAHEART will employ an integrative approach to bring all these research fields under one umbrella. The working groups focus on their topics but benefit from the expertise of the other WGs to overcome scientific and methodological boundaries and boost cardiovascular drug development.
Impact of metabolic disorders on substrate and intermediary metabolism in cardiac myocytes
There is a long-standing concept that the failing heart is an engine out of fuel, but it remains unclear whether substrate utilization alterations and energetic deficits alone cause contractile dysfunction or if associated metabolic intermediates induce maladaptive cardiac remodeling. Metabolic intermediates can modify the function of cardiac proteins, and disruptions in ion handling and energy coupling increase oxidative stress, impairing cardiac function further.
Metabolic aspects of vascular dysfunction
Metabolic diseases are significant risk factors for vascular dysfunction. Macroangiopathy leading to myocardial ischemia and infarction typically results in HFrEF, while microvascular dysfunction is particularly relevant in HFpEF. The relationship between coronary blood flow and HF is bidirectional; reduced coronary blood flow impairs contractile function, and HF, in turn, impairs coronary blood flow.
Immunometabolism: how metabolic alterations control inflammation and vice versa
Metabolism and immunity are tightly interlinked, with inflammation playing a key role in atherosclerosis and myocardial remodeling during HF development.
Mechano-energetic uncoupling and mitochondrial redox alterations
Coupling of cardiac mechanics to metabolism, mediated by cytosolic and mitochondrial ion handling and adenosine diphosphate, is disrupted in various forms of HF, increasing mitochondrial reactive species that hamper excitation-contraction coupling and activate redox-sensitive, maladaptive signaling pathways. Interventions that reduce mitochondrial ROS or their negative impact on mitochondrial function improve survival and function of preclinical HF models. Therefore, the tight interplay between metabolic disorders, mitochondrial dysfunction and EC coupling in HFrEF vs. HFpEF remains to be better investigated.
Communication and Dissemination
The results of EU-METAHEART will be disseminated to the scientific audience and communicated to the general public to increase the awareness of the advances in the search for the treatment and prevention of cardiovascular diseases and heart failure.