Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition Via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jul 29

PMID 37511521

Authors

Xiaomeng Gao

Jingyue Chang

Yi Chang

Lili Fan

Ziqian Liu

Cuijuan Zhang

Tatsuo Shimosawa

Fan Yang

Qingyou Xu

Affiliations

Soon will be listed here.

Abstract

Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix. Aldosterone stimulates mineralocorticoid receptor (MR) activation and induces inflammation, which is important for angiogenesis. Clinically, MR blockers (MRBs) have a protective effect on damaged kidneys, which may be associated with inhibition of angiogenesis. In this study, we used aldosterone-infused mice and found that aldosterone induced angiogenesis and that endothelial-mesenchymal transition (EndMT) in neovascular endothelial cells was involved in renal fibrosis. Notably, aldosterone induced inflammation and stimulated macrophages to secrete vascular endothelial growth factor (VEGF) A to regulate angiogenesis by activating MR, whereas EndMT occurred in response to transforming growth factor-β1 (TGF-β1) induction and participated in renal fibrosis. These effects were antagonized by the MRB esaxerenone. These findings suggest that reducing angiogenesis may be an effective strategy for treating renal fibrosis.

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