Beta-carotene and arachidonic acid induced DNA methylation and the regulation of pro-chemotactic activity of endothelial cells and its progenitors

J Physiol Pharmacol. 2007 Dec;58(4):757-66.

Abstract

DNA methylation is one of the important mechanisms regulating gene expression. Since beta-carotene (BC) was shown to have pro-chemotactic activity and stimulates expression of pro-angiogenic genes, this study was undertaken to define the possible changes in DNA methylation in endothelial cell and its progenitors in the presence of BC. The culture medium for human umbilical vein endothelial cells (HUVEC) and endothelial progenitor cells (EPC) was supplemented with BC (1 - 10 microM) with the presence of arachidonic acid (AA) (3 microM). Global DNA methylation tended to be lower in both endothelial cell lines, after incubation with BC and AA. HUVEC incubated with AA demonstrated the lowest DNA methylation. The decrease of DNA methylation in EPC, induced by BC, was concentration-dependent. The microarray study revealed, that the angiogenesis and homing-related genes were mostly influenced by BC and AA in investigated cells. Our results indicate that BC and AA-induced DNA hypomethylation in EPC and HUVEC, might be a mechanism which may alter gene expression in endothelial cells what in certain conditions may be connected with the suggested pro-malignant effect of this compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Angiogenesis Inducing Agents / pharmacology*
  • Arachidonic Acid / pharmacology*
  • Arachidonic Acid / physiology
  • Cell Line
  • Cell Proliferation
  • Chemotaxis / drug effects*
  • Chromatography, High Pressure Liquid
  • DNA Methylation*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / physiology
  • Endothelium, Vascular / cytology
  • Gene Expression Regulation
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Stem Cells / drug effects*
  • Stem Cells / physiology
  • beta Carotene / pharmacology*
  • beta Carotene / physiology

Substances

  • Angiogenesis Inducing Agents
  • beta Carotene
  • Arachidonic Acid