EN
Role of the mineralocorticoid receptor in Takotsubo stress cardiomyopathy (RP11)
Principal Investigators
Project Summary and Goals
Takotsubo cardiomyopathy (“Broken Heart Syndrome”) is an acute cardiac dysfunction triggered by severe stress. Catecholamine excess activates the renin–angiotensin–aldosterone system (RAAS), causing myocardial injury and heart failure. Since current therapies lack specificity, use of novel mineralocorticoid receptor (MR) antagonists represent a promising strategy, yet the precise role of cell-specific MR activation remains unknown.
Our lab established a preclinical isoproterenol-induced murine model that recapitulates acute myeloid cell infiltration, ventricular dysfunction, and cardiac fibrosis. This project utilizes MR antagonists, conditional cell-specific MR knockouts, and subcellular cAMP biosensor imaging to test if MR blockade in specific microdomains reduces cardiac injury.
The opportunity: This project offers a cutting-edge translational platform to dissect cellular and subcellular MR signaling. As a researcher, you will use advanced in vivo models and molecular techniques to identify novel therapeutic targets, contributing directly to the future of cardiovascular medicine.
Aims Addressed by the Doctoral Candidates
- Evaluate pharmacological MR blockade (spironolactone, finerenone) on cardiac function, inflammation, and fibrosis in stress-induced cardiomyopathy.
- Elucidate the cell-specific roles of the MR in myeloid cells and cardiomyocytes during stress-induced cardiomyopathy using knockout models.
- Analyze subcellular MR signaling within distinct microdomains and its impact on cardiac regulation under stress conditions.
Key Techniques
- Animal model of isoprenalin-induced cardiomyopathy
- Cell-specific in vivo knockout studies: cell-specific Cre mouse lines to induce conditional MR deletion in myeloid cells and cardiomyocytes
- Evaluation of cardiac function (echocardiography, electrocardiogram), structure (histology, fibrosis markers), and inflammation (flow cytometry)
- Förster resonance energy transfer (FRET) biosensors
- Cellular electrophysiology (patch-clamp, microrelectrode, MEA, electrical mapping)
Animal models of heart failure - Functional imaging (confocal, optical mapping, Ca2+ and contractility mapping)
Publications
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Specific Activation of the Alternative Cardiac Promoter of Cacna1c by the Mineralocorticoid Receptor. Mesquita TR, Auguste G, Falcón D, Ruiz-Hurtado G, Salazar-Enciso R, Sabourin J, Lefebvre F, Viengchareun S, Kobeissy H, Lechène P, Nicolas V, Fernandez-Celis A, Gómez S, Lauton Santos S, Morel E, Rueda A, López-Andrés N, Gómez AM, Lombès M, Benitah JP (2018). Circ Res. 122:e49-e61. -
Mosaic theory revisited: inflammation and salt play a central role in arterial hypertension. Hengel F, Benitah JP, Wenzel UO (2022). Cell Mol Immunol. 19:561-576. -
The role of the mineralocorticoid receptor in immune cells in in cardiovascular disease. van der Heijden CD, Bode M, Riksen NP, Wenzel UO (2022). Br J Pharmacol. 179:3135-3151. -
From Tigerstedt to Calcium Oscillations: A Remarkable Journey in Renin Research. Dreher L, Danser AHJ, Wenzel UO (2025). Circ Res. 137:1069-1071 -
Beyond Spironolactone: Does Next Generation of Aldosterone Blockade Add Value? Li S, Dreher L, Danser AHJ, Wenzel UO (2026). Hypertension. 83:e26376.