Atorvastatin downregulates BMP-2 expression induced by oxidized low-density lipoprotein in human umbilical vein endothelial cells

Circ J. 2008 May;72(5):807-12. doi: 10.1253/circj.72.807.

Abstract

Background: Bone morphogenetic protein-2 (BMP-2) plays a key role both in vascular development and pathophysiological processes. However, the effects of oxidized low-density lipoprotein (ox-LDL) combined with atorvastatin on BMP-2 expression are entirely unknown in human umbilical vein endothelial cells (HUVECs). The present study investigates the effects of ox-LDL on BMP-2 expression. Furthermore, the influence of atorvastatin on ox-LDL-induced BMP-2 expression is also examined.

Methods and results: The HUVECs were treated by ox-LDL or combined with pyrrolidine dithiocarbamate (PDTC) or atorvastatin. The expression level of BMP-2 mRNA was examined by real-time PCR and RT-PCR analysis. The expression of BMP-2 protein was assayed by enzyme-linked immunosorbent assay. The malondialdehyde (MDA) and activities of total superoxide dismutase (SOD) were detected by routine methods. The activation of nuclear factor kappaB (NF-kappaB) in HUVECs was determined using an assay kit from active motif and western blot analysis. Ox-LDL treatment significantly increased BMP-2 expression, which is associated with NF-kappaB activation, but BMP-2 expression was suppressed by treatment with PDTC or atorvastatin. Furthermore, the increase in MDA levels and decrease in activities of total SOD caused by ox-LDL treatment were reversed by the treatment of PDTC or atorvastatin.

Conclusions: Ox-LDL-induced BMP-2 expression was suppressed by PDTC or atorvastatin treatment. The effects of atorvastatin might contribute to the mechanisms by inhibiting NF-kappaB activation.

MeSH terms

  • Antioxidants / pharmacology
  • Atorvastatin
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / metabolism
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Down-Regulation / drug effects
  • Drug Interactions
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Gene Expression / drug effects
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lipoproteins, LDL / pharmacology*
  • Malondialdehyde / metabolism
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • Pyrroles / pharmacology*
  • RNA, Messenger / metabolism
  • Superoxide Dismutase / metabolism
  • Thiocarbamates / pharmacology
  • Transcription Factor RelA / metabolism
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism
  • Umbilical Veins / cytology

Substances

  • Antioxidants
  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • Pyrroles
  • RNA, Messenger
  • Thiocarbamates
  • Transcription Factor RelA
  • Transforming Growth Factor beta
  • oxidized low density lipoprotein
  • prolinedithiocarbamate
  • Malondialdehyde
  • Proline
  • Atorvastatin
  • Superoxide Dismutase