Depression is a common and serious comorbidity of cardiovascular disease (CVD) affecting one in three patients, among which women earlier and more frequently. Depression increases the risk for CVD development, acute events and mortality by >2 fold, independently of traditional risk factors, and constitutes an enormous socioeconomic burden in terms of morbidity, mortality and healthcare costs. Still, the patients at risk, disease trajectories and causative mechanisms involved remain unknown. TO_AITION addresses the hypothesis that immune-metabolic dysregulation, occurring as a result of genetic, lifestyle and environmental risk factors ‘training’ innate immunity, drives low grade systemic inflammation leading to the development of CVD-depression comorbidity. It integrates basic (cell models, immune-metabolic mechanisms, myeloid cell reprogramming), preclinical (animal models, CRISPR genome editing) and clinical (longitudinal cohorts with comprehensive existing data) research, in order to characterise immune-metabolic mechanisms driving CVD-depression comorbidity. Both hypothesis and data-driven strategies will be employed to address causality, focusing on genetic, epigenetic, transcriptional, metabolic and other disturbances leading to the development of comorbidity. Drug-drug interactions and their effects on causative mechanisms and disease trajectories will also be determined. Pathways identified will be evaluated in cell-based and animal models to prove their causal role and obtain mechanistic insight. Finally, new risk models will be developed, and relevant regulatory, cost-effectiveness and feasibility issues addressed. Effective patient-oriented awareness actions, dissemination, exploitation and management activities are also provisioned. TO_AITION will therefore rationally change our current understanding of the causative mechanisms driving CVD-depression comorbidity, unravelling patients’ complexity and improving their diagnosis, monitoring and management.

Immune-mediated diseases (IMDs) are increasing rapidly in the developed countries constituting a huge medical, economic and societal challenge. The reasons to this epidemic are not known, but exposome needs to play an important role since genetic factors cannot explain such a rapid change. In the HEDIMED project altogether 20 academic and industrial partners will join their multidisciplinary and supplementary forces to identify exposomic determinants which are driving this epidemic. The project is based on a combination of data and biological samples from large clinical cohorts constituting the largest clinical resource in this field including 350.000 pregnant women, 28.000 children prospectively followed from birth and 6.600 children from cross-sectional studies. HEDIMED focuses on common chronic IMDs that cause a significant disease burden, including type 1 diabetes, celiac disease, allergies and asthma. Exposomic disease determinants and the underlying biological pathways will be identified by exploratory approach using advanced omics and multiplex technologies combined with cutting–edge datamining technologies. Particular emphasis is paid on early fetal and childhood exposome since the disease process is known to start early. Inclusion of several IMDs makes it possible to identify determinants that are common for many IMDs facilitating the development of widely operating treatments. HEDIMED includes also data and samples from clinical trials that have used exposomice interventions and cell and organ culture models to help the identification of causal associations. HEDIMED will generate an open-access toolbox that offers various kind of data, new technologies, interactions forums, latest information and functional tools for several stakeholders to facilitate the efforts to find ways to control the IMD epidemic. HEDIMED will generate several innovations which can become exploited widely in diagnostic, therapeutic, preventive and health-economical applications. HEDIMED will work together with the other projects (EXPANSE, HEAP, ATHLETE, EQUAL-LIFE, LONGITOOLS, EPHOR, REMEDIA and EXIMIOUS) funded within the Human Exposome programme call H2020 SC1-BHC-2018-2020, in order to achieve collaboration and synergy