Project description
Investigating mechanisms in CVD-depression comorbidity
Depression is highly associated with cardiovascular disease (CVD), significantly increasing the risk of CVD development, acute events and mortality, especially in women. As a consequence, it represents a social and economic issue affecting the patient’s life and causing healthcare costs to rise. However, the mechanisms and progression of the disease remain unknown. The EU-funded TO_AITION project works on the hypothesis that immune-metabolic dysregulation due to genetic, lifestyle and environmental risk factors affects immunity mechanisms leading to CVD-associated depression. The project will effectuate basic, preclinical and clinical research applying data-driven strategies to detect and describe immune-metabolic mechanisms responsible for CVD-depression comorbidity, aiming to improve diagnosis and management of the disease.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
115 27 Athina
Greece