Project Details
Projekt
Regulation, Diagnostics and Therapy focusing on the mineralocorticoid receptor involved in cardiac remodelling
Subject Area
Cardiology, Angiology
Term
from 2015 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 284194617
The incidence of heart failure (HF) is increasing because of ageing of the population, while the prevalence at least of systolic HF is also increasing because of improved survival, as a result of life saving therapies. Despite optimal therapy, patients with HF experience disease progression associated with high mortality rates. HF is still the first cause of hospital admission in subjects aged>65 years. The obvious solution for HF epidemics is to prevent new onset HF with therapies directed specifically to mechanistic targets that are involved in the transition to HF. The mineralocorticoid receptor (MR) and its natural ligand, the hormone Aldosterone (Aldo), play important roles during cardiac and arterial remodeling, but the underlying effects are still not understood. MR antagonists are highly recommended for treatment of systolic symptomatic HF, and potentially for HF with preserved ejection fraction. However, adverse effects limit their use in clinical practice. Upstream, MR expression level and activity are modulated by genetic (functional polymorphisms) and epigenetic (miRNA, DNA methylation) features. This could participate to MR activation in HF but this has never been explored. The French and German Partners of this application have identified Neutrophil Gelatinase-Associated Lipocalin (NGAL), Galectin-3 (Gal-3) and specific non-coding RNAs such as microRNAs (miRNAs) as highly focused targets controlling downstream key MR mediated HF mechanisms. Therefore, interfering with mechanistic pathways involved in upstream and/or downstream MR activation may provide therapeutic alternatives to MRAs.
DFG Programme
Research Grants
International Connection
France
Partner Organisation
Agence Nationale de la Recherche / The French National Research Agency
Cooperation Partner
Professor Faiez Zannad, Ph.D.
