IN CONTROL II

2019

The IN-CONTROL II consortium builds upon the success of IN-CONTROL I, which highlighted the pivotal role of the microbiome in low-grade inflammation associated with atherosclerotic cardiovascular diseases (CVD) and related risk factors such as lipid levels and microbiome-derived metabolites. These insights are crucial for addressing the rising rates of CVD-related mortality, particularly in aging and overweight populations.

The Focus
The objectives of IN-CONTROL II are to:

  • Investigate the mechanisms underlying trained immunity in CVD patients, considering factors like senescence, age, sex, and obesity.
  • Elucidate the interactions between microbiome-derived signals (aromatic amino acids, metabolites, bile acids) and immune senescence in obesity-related cardio-metabolic diseases.
  • Identify novel therapeutic targets and develop pharmacological and microbiome-based therapies to counteract inappropriate induction of trained immunity and inflammation in cardiovascular disease.

The Research
The consortium aims to shift from association to causality, from population-based cohorts to patient groups with atherosclerotic cardiovascular disease (CVD) and from observation to intervention. In this transition, it will also take advantage of recent developments in the network of the consortium, delineating cellular senescence as a druggable target for the broad spectrum of age-related chronic diseases, including cardiovascular diseases, and identification of components of the bile acid-signaling system for this purpose. Another recent development of the recognition of innate immune memory (‘trained immunity’) as pathophysiological mechanism in atherosclerotic CVD.

The consortium will conduct proof-of-principle trials in specific patient cohorts, employing advanced experimental techniques such as systems biology, single cell sequencing, innovative animal models, and metabolic flux quantification (fluxomics). A talent program will facilitate knowledge transfer and skill development for young researchers within the consortium, emphasizing rapid translation of research findings into clinical applications.

Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.

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PERFECT-FIT

2020
Smoking tobacco and physical inactivity are key preventable risk factors of cardiovascular disease (CVD). Perfect Fit aims to prevent CVD, promote well-being, and reduce healthcare costs, particularly targeting disadvantaged populations where smoking and physical inactivity are prevalent. The Research The project develops tailored, evidence-based, near real-time computer coaching for quitting smoking and enhancing PA. For every individual, a personal model is designed which generates personalized recommendations based on high-quality existing and newly collected data, and adapts to changing circumstances/progress (similar to a TomTom navigation system), using machine learning techniques and incorporating domain-specific expert knowledge (e.g. health behaviour change strategies). Virtual coaches (VCs) communicate advice in a motivating way that fits individuals’ persuasive communication styles. Perfect Fit integrates big-data science, sensor technology, and personalized real-time feedback to support smoking cessation and promote adequate physical activity (in both gym settings and daily life). The key questions of this study are: Which adaptivity is needed to create a robust, safe, and effective interaction between individuals and machines? How can we develop advanced data science methods and embed this in current smoking cessation and PA coaching practice? How do measurement modalities, feedback and communication affect individuals’ smoking status and PA? Origin This project was funded within the Big Data & Health Program. The focus of this public-private research program is the use of big data for the early detection and prevention of cardiovascular diseases. The program has been developed by NWO, ZonMw, the Dutch Heart Foundation, the Top Sectors Life Sciences & Health (LSH), ICT and Creative Industry, the Ministry of Health, Welfare and Sport, and the Netherlands eScience Center. Within this research program, the ambitions of the Dutch Heart Foundation, the Ministry of Health, Welfare and Sport, and the Netherlands eScience Center were aligned with the ambitions of Commit2Data for the Top Sectors ICT, LSH, and Creative Industry, as described in the 2018-2019 Kennis- en Innovatiecontracts between NWO and the Top Sectors.
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DOUBLE DOSE

2021
Cardiomyopathies, caused by genetic mutations affecting cardiac muscle components, pose significant economic and societal burdens due to their hereditary nature and early onset. Despite known genetic defects, predicting disease progression remains challenging due to extreme clinical variability. Recent research indicates that cardiomyopathy mutations induce metabolic stress, exacerbated by factors like obesity, which can accelerate disease progression. The Double Dose hypothesis suggests that targeting metabolic stress may offer preventive or curative strategies for these conditions. The Focus The Double Dose Consortium aims to understand how cardiomyopathy-causing mutations lead to structural changes in cardiomyocytes. This interdisciplinary effort combines experts in preclinical research, clinical genetics, health technology assessment, and clinical care focused on cardiomyopathy in both children and adults. The Research The consortium combines experts in preclinical research, clinical genetics, health technology assessment and clinical researchers with a strong clinical focus on cardiomyopathy in children and adults. These experts investigate how obesity and muscle adiposity contribute to vascular and cardiac muscle dysfunction in mutation carriers through the analysis of clinical data, patient samples, and experimental models. They will also study the mechanisms underlying ultrastructural changes in cardiomyocytes caused by these mutations, leading to impaired metabolism, contraction, relaxation defects, and disrupted cellular communication within the heart. Utilizing extensive patient cohorts and ongoing studies, the consortium aims to optimize care for cardiomyopathy patients by assessing the cost-effectiveness of diagnostics and clinical interventions. They plan to translate findings on metabolic alterations into clinical trials targeting treatments that reduce metabolic stress. The Double Dose program will establish biobanks containing serum, tissue, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to provide mechanistic insights into cardiomyopathy pathophysiology and improve diagnosis and care. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation, together with Stichting Hartedroom. The consortium is a continuation of the Dosis consortium, in which the interaction between mutation and external factors was investigated. They found that cardiomyopathy-mutations induce metabolic stress and that secondary metabolic stress, such as obesity accelerates disease progression.  
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