1. Finerenone Reduces Renal RORγt γδ T Cells and Protects against Cardiorenal Damage.
- Author
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Luettges K, Bode M, Diemer JN, Schwanbeck J, Wirth EK, Klopfleisch R, Kappert K, Thiele A, Ritter D, Foryst-Ludwig A, Kolkhof P, Wenzel UO, and Kintscher U
- Subjects
- Animals, Blood Pressure, Desoxycorticosterone Acetate, Fibrosis, Kidney pathology, Male, Mice, Mice, Inbred C57BL, Nuclear Receptor Subfamily 1, Group F, Member 3 therapeutic use, Hypertension drug therapy, Hypertension, Renal pathology, Naphthyridines pharmacology, T-Lymphocytes
- Abstract
Introduction: Chronic activation of the mineralocorticoid receptor (MR) leads to pathological processes like inflammation and fibrosis during cardiorenal disease. Modulation of immunological processes in the heart or kidney may serve as a mechanistic and therapeutic interface in cardiorenal pathologies. In this study, we investigated anti-inflammatory/-fibrotic and immunological effects of the selective nonsteroidal MR antagonists finerenone (FIN) in the deoxycorticosterone acetate (DOCA)-salt model., Methods: Male C57BL6/J mice were uninephrectomized and received a DOCA pellet implantation (2.4 mg/day) plus 0.9% NaCl in drinking water (DOCA-salt) or received a sham operation and were orally treated with FIN (10 mg/kg/day) or vehicle in a preventive study design. Five weeks after the procedure, blood pressure (BP), urinary albumin/creatinine ratio (UACR), glomerular and tubulointerstitial damage, echocardiographic cardiac function, as well as cardiac/renal inflammatory cell content by FACS analysis were assessed., Results: BP was significantly reduced by FIN. FACS analysis revealed a notable immune response due to DOCA-salt exposure. Especially, infiltrating renal RORγt γδ-positive T cells were upregulated, which was significantly ameliorated by FIN treatment. This was accompanied by a significant reduction of UACR in FIN-treated mice. In the heart, FIN reduced DOCA-salt-induced cardiac hypertrophy, cardiac fibrosis and led to an improvement of the global longitudinal strain. Cardiac actions of FIN were not associated with a regulation of cardiac RORγt γδ-positive T cells., Discussion/conclusion: The present study shows cardiac and renal protective effects of FIN in a DOCA-salt model. The cardiorenal protection was accompanied by a reduction of renal RORγt γδ T cells. The observed actions of FIN may provide a potential mechanism of its efficacy recently observed in clinical trials., (© 2022 S. Karger AG, Basel.)
- Published
- 2022
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