Mineralocorticoid Receptors as Key Regulators of Cardiac Lesions (A05 (P05))

• Subject Area: Cardiology, Angiology ; Pharmacology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

Based on our findings from the first funding period, we will continue to study mineralocorticoid receptor (MR) functions in the heterocellular heart. In a bedside-to-bench approach, we will investigate which molecular processes are involved in the reversal of cardiac remodelling upon pharmacological MR blockade in mice. We will use single nucleus RNA-seq to compare the effects of pharmacological MR blockade and MR gene targeting on cell type-specific gene expression, predict heterocellular interactions, and thus assess how MR activity in one cell type influences other cardiac cells. Conversely, we will explore how MR activity is modulated by co-regulators in a cell type-, ligand-, and context-sensitive manner. We will evaluate the therapeutic potential of the identified downstream mediators and co-regulators of MR as new pharmacological targets in gain- and loss-of-function experiments. By comparing cardiac cell types to kidney epithelial cells, we aim to pave the way towards organ-selective targeting of the MR signalling pathway.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1425: Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Head: Privatdozent Dr. Achim Lother