Effects of probucol on angiotensin II-induced BMP-2 expression in human umbilical vein endothelial cells

Mol Med Rep. 2013 Jan;7(1):177-82. doi: 10.3892/mmr.2012.1145. Epub 2012 Oct 24.

Abstract

Bone morphogenetic protein-2 (BMP-2) participates significantly in vascular development and pathophysiological processes. Angiotensin II (AngII) has been demonstrated to be critical in the initiation and progression of atherosclerosis. However, the effects of AngII on BMP-2 expression and of probucol on the AngII-induced BMP-2 expression in human umbilical vein endothelial cells (HUVECs) are unknown. The aim of our study was to investigate these effects. HUVECs were cultured and stimulated with various agents. The total superoxide dismutase (SOD) activity and the concentrations of malondialdehyde (MDA) and BMP-2 were measured by standard methods. Northern blotting was used to detect the expression of BMP-2 mRNA. The activation of NF-κB in the HUVECs was also determined. The AngII treatment significantly increased BMP-2 expression levels and activated NF-κB. These effects were suppressed by treatment with pyrrolidine dithiocarbamate (PDTC) or probucol. Furthermore, the increased levels of MDA in the conditioned medium and the decrease in the total SOD activity caused by the AngII treatment were reversed by treatment with probucol or PDTC. Probucol downregulated the AngII‑induced BMP-2 expression. These effects of probucol may be mediated by the inhibition of NF-κB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Anticholesteremic Agents / pharmacology*
  • Bone Morphogenetic Protein 2 / genetics*
  • Bone Morphogenetic Protein 2 / metabolism
  • Gene Expression Regulation / drug effects*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Immunohistochemistry
  • Intracellular Space / metabolism
  • Probucol / pharmacology*
  • Protein Transport / drug effects
  • Superoxide Dismutase / metabolism
  • Transcription Factor RelA / metabolism

Substances

  • Anticholesteremic Agents
  • Bone Morphogenetic Protein 2
  • Transcription Factor RelA
  • Angiotensin II
  • Superoxide Dismutase
  • Probucol