Related Experiment Video

Updated: Jan 27, 2026

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Homocysteine-induced inverse expression of tissue factor and DPP4 in endothelial cells is related to NADPH oxidase

H I Korkmaz1,2, N E Hahn1,2, K M Jansen1

  • 11 Department of Pathology, Amsterdam UMC, VUmc , Amsterdam, The Netherlands.

Physiology International
|March 20, 2019
PubMed

Insights

Homocysteine (Hcy) increases tissue factor (TF) and decreases dipeptidyl peptidase IV (DPP4) in endothelial cells. This inverse relation is dependent on NADPH oxidase (NOX)-mediated reactive oxygen species (ROS) production.

Area of Science:

  • Endothelial cell biology
  • Cardiovascular research
  • Biochemistry

Background:

  • Homocysteine (Hcy) is linked to endothelial cell apoptosis and increased NADPH oxidase (NOX) activity.
  • Loss of dipeptidyl peptidase IV (DPP4) expression correlates with tissue factor (TF) induction in ischemic endothelial cells.
  • Hcy can initiate thrombosis via TF induction.

Purpose of the Study:

  • To investigate if the inverse relationship between TF and DPP4 expression is Hcy-dependent.
  • To determine the role of NOX-mediated reactive oxygen species (ROS) in this Hcy-induced effect.

Main Methods:

  • Human umbilical vein endothelial cells (HUVECs) were exposed to Hcy (2.5 mM) for 3 and 6 hours.
  • Digital-imaging microscopy was used to assess DPP4 and TF expression.
  • NOX2/p47phox-mediated nitrotyrosine (ROS) production was quantified.

Main Results:

  • Hcy significantly increased TF expression and decreased DPP4 expression in HUVECs after 6 hours.
  • Hcy also significantly increased NOX2 and p47phox subunits, coinciding with nitrotyrosine (ROS) expression.
  • Apocynin, a NOX inhibitor, reduced Hcy-induced effects on ROS, TF, and DPP4.

Conclusions:

  • The inverse relationship between TF and DPP4 in endothelial cells is indeed Hcy-dependent.
  • NOX activity and subsequent ROS production are critical mediators of this Hcy-induced effect.
Abstract

Keywords:
DPP4NADPH oxidaseendothelial cellshomocysteinetissue factor

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