Hypercholesterolaemic serum increases the permeability of endothelial cells through zonula occludens-1 with phosphatidylinositol 3-kinase signaling pathway

J Biomed Biotechnol. 2009;2009:814979. doi: 10.1155/2009/814979. Epub 2010 Jan 27.

Abstract

Purpose: Hypercholesterolemia and tight junctions play important roles in atherosclerosis. But the relationship between these two factors is unclear. In the present study, we investigated whether hypercholesterolemic serum could change the permeability of endothelial cells through altering expression and/or distribution of tight junction protein zonula occludens-1 (ZO-1). Phosphatidylinositol 3-kinase (PI3K) signaling pathway was also examined.

Materials and methods: Cultured endothelial cells were treated with different concentration levels of hypercholesterolemic serum. The expression and distribution of ZO-1, the permeability of cultured cells and the involvement of PI3K signaling pathway were measured by various methods.

Results: In the present study, we found that hypercholesterolemic serum could not change the expression of ZO-1 either in mRNA or protein level. However, hypercholesterolemic serum could change the distribution of ZO-1 in cultured endothelial cells, and increase the permeability with a dose-dependent manner. When PI3K specific inhibitor wortmannin was used, the effects induced by hypercholesterolemic serum could be partly reversed. The role of PI3K signaling pathway was further confirmed by PI3K activity assay.

Conclusions: Our results suggested that although hypercholesterolemic serum could not change the expression of ZO-1, it could change the distribution and increase the permeability in endothelial cells through PI3K signaling pathway.

MeSH terms

  • Animals
  • Cell Membrane Permeability* / drug effects
  • Cholesterol / administration & dosage
  • Cholesterol / blood
  • Cholesterol / pharmacology
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypercholesterolemia / blood*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Signal Transduction* / drug effects
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism
  • Zonula Occludens-1 Protein

Substances

  • Dietary Fats
  • Membrane Proteins
  • Phosphoproteins
  • RNA, Messenger
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Cholesterol
  • Phosphatidylinositol 3-Kinases