2. Academic Validation
  3. Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice

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

  • Int J Mol Sci. 2023 Jul 21;24(14):11766. doi: 10.3390/ijms241411766.
Xiaomeng Gao 1 2,  Jingyue Chang 1 2,  Yi Chang 2 3,  Lili Fan 1 2,  Ziqian Liu 1 2,  Cuijuan Zhang 2 3,  Tatsuo Shimosawa 4,  Fan Yang 2 3,  Qingyou Xu 1 2 3
Affiliations

Affiliations

  • 1 Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
  • 2 Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
  • 3 Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
  • 4 Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare, Narita 286-8686, Japan.
PMID: 37511521 DOI: 10.3390/ijms241411766
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.

Keywords

VEGFA; aldosterone; angiogenesis; mineralocorticoid receptor blocker; renal fibrosis.

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