FORSEE

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.

CardioResource will be the first national registry for patients with hereditary cardiac conditions. By making available, amongst others, clinical data, imaging, and genetic data of all seven largest Dutch University Medical Centers, CardioResource will enable breakthrough research into these disorders. This will lead to more accurate diagnosis and improved understanding of the risk of developing disease and severe complications for patients and their families. It will also facilitate the development of novel therapies for more effective and targeted treatment of these life-threatening conditions. The research Over the past few decades, researchers have made significant progress in identifying inherited heart diseases. In many cases, these conditions can be traced to a defect in a single gene. However, for approximately half of patients, the underlying genetic cause remains unclear because it often involves variations in multiple genes, combined with other clinical, acquired, and/or lifestyle factors. Understanding how these factors conspire to determine disease risk and severity necessitates access to larger and comprehensive datasets. A vast amount of patient data is already available within the university medical centers (UMCs). However, these data are stored in separate systems at each institute and are therefore fragmented and inaccessible for research. CardioResource aims to address this challenge by harmonizing data across UMCs and making them available for research through a national research infrastructure, in a privacy-preserving manner. To achieve this, CardioResource is developing an innovative data infrastructure based on the FAIR principles: Findable, Accessible, Interoperable, and Reusable. The platform will be continuously updated with the latest patient information, creating a sustainable resource for cardiovascular research nationwide. The origin The Dutch research community has a long-standing track record in the field of inherited cardiac conditions. Over the years, numerous databases have been established for individual studies. However, the manual development and maintenance of these databases require substantial time and effort. To address this challenge, the community came up with the idea for CardioResource. The NWO Research Infrastructure program for national consortia provided the opportunity to finance the CardioResource project. The initiative brings together all seven Dutch UMCs, the NLHI, NHR, Dutch Heart Foundation, Hartekind Foundation, DCVA, and Health-RI. This broad partnership reflects the national need to strengthen cardiovascular data infrastructure and aligns with the ambitions of the DCVA and Health-RI to enable FAIR and reusable health data. Multidisciplinary teams across the participating UMCs will jointly establish the infrastructure. This close collaboration is essential for creating a sustainable and valuable resource that will ultimately benefit patients with inherited cardiac conditions.