SECRETE-HF SIGNED

Project "SECRETE-HF" data sheet

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 Project objective

The objective of SECRETE-HF is to demonstrate the effects of secreted factors from failing hearts to explain the etiology of multimorbidity in heart failure (HF). The project focuses on two co-morbid patterns: 1) the emerging susceptibility of HF patients for incident cancer, 2) the more established co-morbid conditions of renal, liver and pulmonary disease in HF. The rationale is: • HF treatment has improved, yet morbidity and mortality remain high, which can be attributed to co-morbid conditions rather than pump failure alone. • HF treatment is heart-oriented, neglecting the systemic effects that come with HF, and the associated morbidity and mortality. • Using innovative experimental approaches such as organ transplant models, target finding, and deep phenotyping of clinical databases I will dissect HF-derived effects on tumor growth and organ damage. OBJECTIVES 1. To establish the effects of HF, due to different etiologies, using the state-of-the-art heart transplantation murine model with (spontaneous) formation of colon and renal tumors, and phenotype tumor growth, as well as the main HF-affected organs: kidney, liver and lungs. 2. Identification of the cardiac secretome using unbiased approaches. 3. Integrate the results and identify overlapping and diverse factors from different HF forms, and their consequences for tumor growth and kidney/liver/lung remodeling. 4. Validate discoveries in human cohorts with data on incident HF, cancer and organ function. 5. Create clinical algorithms to detect, monitor and act on extra-cardiac disease. WORKPACKAGES WP 1: Create HF, murine heart transplantation models; phenotype tumor growth and organ involvement. WP 2: Explore the proteomic, metabolomic and extracellular vesicle profiles from HF subforms. WP 3: Validate secreted factors in vitro and in vivo. WP 4: Validate human relevance in large population-based cohorts with unique phenotyping. WP 5: Describe added value of novel markers and design clinical