Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction

Diab Vasc Dis Res. 2015 Jul;12(4):290-7. doi: 10.1177/1479164115583192. Epub 2015 May 11.

Abstract

Pro-inflammatory conditions induced by products of protein glycation in diabetes substantially enhance the risk of endothelial dysfunction and related vascular complications. Endothelial cell specific molecule-1 (ESM-1) or endocan has been demonstrated as a potential biomarker in cancer and sepsis. Its role in diabetes-induced pathologies remains unknown. The expression of ESM-1 gene is under cytokine regulation, indicating its role in endothelium-dependent pathological disorders. In this study, we investigated the effect of advanced glycated human serum albumin (AGE-HSA) on the production of ESM-1. We show that AGE-HSA exerts a modulating role on the expression of ESM-1 in human umbilical vein endothelial cells. It up-regulates expression of ESM-1 protein in a dose-dependent manner which correlates with its messenger RNA (mRNA) transcription. RAGE and galectin-3, both AGE receptors, show antagonistic action on its expression. While gene silencing of RAGE has down-regulatory effect, that of galectin-3 has up-regulatory effect on AGE-induced expression of ESM-1. Inhibition of MAPKKK and JNK pathways did not alter the expression. In contrast, phosphatidylinositol 3 kinase (PI3K) inhibition significantly up-regulated ESM-1 expression. In conclusion, these results suggest that AGE-induced activation of human umbilical vein endothelial cells promotes formation of endocan which is an endothelial dysfunction marker and may be related to vascular disease in diabetes.

Keywords: Endothelial cell specific molecule-1; advanced glycation end product; diabetes; galectin-3; serum albumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / physiopathology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Galectin 3 / drug effects
  • Galectin 3 / metabolism
  • Glycated Serum Albumin
  • Glycation End Products, Advanced / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Kinase Kinases / drug effects
  • MAP Kinase Kinase Kinases / metabolism
  • Neoplasm Proteins / drug effects*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteoglycans / drug effects*
  • Proteoglycans / genetics
  • Proteoglycans / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor for Advanced Glycation End Products / drug effects
  • Receptor for Advanced Glycation End Products / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Albumin / pharmacology*
  • Signal Transduction

Substances

  • AGER protein, human
  • ESM1 protein, human
  • Galectin 3
  • Glycation End Products, Advanced
  • Neoplasm Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteoglycans
  • Receptor for Advanced Glycation End Products
  • Serum Albumin
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • Glycated Serum Albumin