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Empagliflozin reduces left ventricular mass increase and improves cardiomyocyte hypertrophy after 5/6 nephrectomy

Chen X, Wohnhaas CT, Delić D, Schommer N, Duerschmied D, Cao Y, Zhang Z, Reichetzeder C et al.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2025

Abstract

Left ventricular hypertrophy (LVH) is a common cardiac complication in patients with cardiorenal syndrome. Empagliflozin has demonstrated cardio-renal protective effects in clinical studies, potentially linked to reductions in left ventricular mass (LVM). Using a 5/6 nephrectomy rat model to induce cardiorenal syndrome, we administered two doses of Empagliflozin (3 mg/kg/day and 15 mg/kg/day) via gavage for 95 days, with Telmisartan as a positive control. Cardiac structure and function were assessed using echocardiography, histological analysis, and serum biomarkers. Single-nucleus RNA sequencing (snRNA-seq) and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to investigate molecular mechanisms. The 5/6 nephrectomy increased serum creatinine, troponin T, LVM, ejection fraction, and cardiomyocyte diameter. Empagliflozin treatment significantly decreased LVM and cardiomyocyte hypertrophy, comparable to Telmisartan. snRNA-seq revealed no changes in major cardiac cell populations but identified differential expression of cardiomyocyte development genes, including Fhl2, Tbx20, and Angpt1. qRT-PCR data for Fhl2 and Tbx20 aligned with the snRNA-seq data, showing that Empagliflozin increased Fhl2 expression and decreased Tbx20 expression. Immunofluorescence showed increased myocardial infiltration of M2 macrophages, CD4 + T cells, and CD8 + T cells in Empagliflozin-treated rats, but there was no difference between the 5/6 nephrectomized rats and normal rats.…

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