Thioredoxin-interacting protein promotes high-glucose-induced macrovascular endothelial dysfunction

Xiaoyu Li, Karen L. Kover, Daniel P. Heruth, Dara J. Watkins, Yanchun Guo, Wayne V. Moore, Luke G. He, Mengwei Zang, Mark A. Clements, Yun Yan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Thioredoxin-interacting protein (TXNIP) emerges as a central regulator for glucose homeostasis, which goes awry in diabetic subjects. Endothelial dysfunction is considered the earliest detectable stage of cardiovascular disease (CVD), a major complication of diabetes. Here, we hypothesize that TXNIP may promote endothelial dysfunction seen in Type 1 diabetes mellitus (T1D). Using a T1D-like rat model, we found that diabetic rats showed significantly higher TXNIP mRNA and protein levels in peripheral blood, compared to their non-diabetic counterparts. Those changes were accompanied by decreased production of nitric oxide (NO) and vascular endothelial growth factor (VEGF), concurrent with increased expression of reactive oxygen species (ROS) and vascular cell adhesion molecule 1 (VCAM-1) in the aortic endothelium. In addition, TXNIP overexpression in primary human aortic endothelial cells (HAECs) induced by either high glucose or overexpression of carbohydrate response element binding protein (ChREBP), a major transcriptional activator of TXNIP, promoted early apoptosis and impaired NO bioactivity. The correlation between TXNIP expression levels and endothelial dysfunction suggests that TXNIP may be a potential biomarker for vascular complications in T1D patients.

Original languageEnglish (US)
Pages (from-to)291-297
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume493
Issue number1
DOIs
StatePublished - Nov 4 2017

Keywords

  • Aortic endothelial cells
  • Cardiovascular disease
  • Diabetes mellitus
  • Endothelial dysfunction
  • TXNIP

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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