Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition: in vitro and in vivo study
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Pei-Rong Lu. Department of Ophthalmology, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China. lupeirong@suda.edu.cn

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Supported by the National Natural Science Foundation in China (No.81671641); Jiangsu Provincial Medical Innovation Team (No.CXTDA2017039); Gusu Health Talents Program (No.GSWS 2022018).

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    Abstract:

    AIM: To provide the direct evidence for the crucial role of trimethylamine N-oxide (TMAO) in vascular permeability and endothelial cell dysfunction under diabetic condition. METHODS: The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells (HRMEC) under high glucose conditions was tested by a cell counting kit, wound healing, a transwell and a tube formation assay. The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction (RT-PCR). The expression of the cell junction was measured by Western blotting (WB) and immunofluorescence staining. In addition, two groups of rat models, diabetic and non-diabetic, were fed with normal or 0.1% TMAO for 16wk, and their plasma levels of TMAO, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested. The vascular permeability of rat retinas was measured using FITC-Dextran, and the expression of zonula occludens (ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining. RESULTS: TMAO administration significantly increased the cell proliferation, migration, and tube formation of primary HRMEC either in normal or high-glucose conditions. RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation, while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment. Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage, which were even higher in TMAO-feeding diabetic rats. Furthermore, TMAO administration increased the rat plasma levels of VEGF, IL-6 and TNF-α while decreasing the retinal expression levels of ZO-1 and claudin-5. CONCLUSION: TMAO enhances the proliferation, migration, and tube formation of HRMEC, as well as destroys their vascular integrity and tight connection. It also regulates the expression of VEGF, IL-6, and TNF-α.

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Jia-Yi Jiang, Wei-Ming Liu, Qiu-Ping Zhang, et al. Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition: in vitro and in vivo study. Int J Ophthalmol, 2024,17(1):25-33

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Publication History
  • Received:March 26,2023
  • Revised:October 30,2023
  • Adopted:
  • Online: December 21,2023
  • Published: