PRECISE

Pulmonary Hypertension (PH), particularly Pulmonary Arterial Hypertension (PAH), presents a fatal complication in chronic diseases, affecting 1 in 50,000 individuals, predominantly at a young age and more often in females. The underlying genetic link involves mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene, disrupting BMP signaling. The PHAEDRA-IMPACT consortium aims to understand PH and PAH. The Research The research focuses on understanding PAH through the transforming growth factor-β (TGFβ) signaling pathway, particularly influenced by mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene, prevalent in heritable and some non-hereditary PAH cases. The PHAEDRA initiative identified compounds that modulate the TGFβ/BMP balance, showing efficacy in restoring endothelial function and reversing pulmonary vascular remodeling in preclinical models, though not curing PAH, making early detection crucial. PHAEDRA has identified biomarkers for timely diagnosis and personalized treatment. PHAEDRA-IMPACT will enhance early detection using non-invasive risk assessments, imaging, and biomarker profiling to detect pre-capillary PH. Precision medicine will guide tailored therapies based on advanced imaging and biomarker analyses, addressing disease progression variability among predisposed individuals. Additionally, patient-derived induced pluripotent stem (iPS) cells will be used in 3D culture models of lung and heart tissues to uncover PAH mechanisms and identify therapeutic targets. This comprehensive approach aims to advance our understanding of PAH pathogenesis, accelerate drug development, and enable personalized treatment and preventive strategies for individuals at risk or affected by PH. 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.