Trimethylamine N-oxide Aggravates Vascular Permeability and Endothelial Cell Dysfunction Under Diabetic Condition: and Study

Overview

Journal Int J Ophthalmol

Specialty Ophthalmology

Date 2024 Jan 19

PMID 38239938

Authors

Jia-Yi Jiang

Wei-Ming Liu

Qiu-Ping Zhang

Hang Ren

Qing-Ying Yao

Gao-Qin Liu

Pei-Rong Lu

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus.

Zhang J, Wang H, Liu Y, Shi M, Zhang M, Zhang H Front Cell Infect Microbiol. 2024; 14:1370999.

PMID: 38660489 PMC: 11039806. DOI: 10.3389/fcimb.2024.1370999.

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