Genome-wide analysis of the endothelial transcriptome under short-term chronic hypoxia. Academic Article Article uri icon

Overview

MeSH

  • Aorta
  • Apoptosis
  • Cells, Cultured
  • Cytoskeletal Proteins
  • DNA, Complementary
  • Energy Metabolism
  • Expressed Sequence Tags
  • Extracellular Matrix Proteins
  • Female
  • Gene Library
  • Heat-Shock Proteins
  • Humans
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Subtraction Technique

MeSH Major

  • Cell Hypoxia
  • Endothelial Cells
  • Endothelium, Vascular
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Transcription, Genetic

abstract

  • We have utilized serial analysis of gene expression (SAGE) to analyze the temporal response of human aortic endothelial cells (HAECs) to short-term chronic hypoxia at the level of transcription. Primary cultures of HAECs were exposed to 1% O2 hypoxia for 8 and 24 h and compared with identical same passage cells cultured under standard (5% CO2-95% air) conditions. A total of 121,446 tags representing 37,096 unique tags were sequenced and genes whose expression levels were modulated by hypoxia identified by novel statistical analyses. Hierarchical clustering of genes displaying statistically significant hypoxia-responsive alterations in expression revealed temporal modulation of a number of major functional gene families including those encoding heat shock factors, glycolytic enzymes, extracellular matrix factors, cytoskeletal factors, apoptotic factors, cell cycle regulators and angiogenic factors. Within these families we documented the coordinated modulation of both previously known hypoxia-responsive genes, numerous genes whose expressions have not been previously shown to be altered by hypoxia, tags matching uncharacterized UniGene entries and entirely novel tags with no UniGene match. These preliminary data, which indicate a reduction in cell cycle progression, elevated metabolic stress and increased cytoskeletal remodeling under acute hypoxic stress, provide a foundation for further analyses of the molecular mechanisms underlying the endothelial response to short-term chronic hypoxia.

publication date

  • June 17, 2004

has subject area

  • Aorta
  • Apoptosis
  • Cell Hypoxia
  • Cells, Cultured
  • Cytoskeletal Proteins
  • DNA, Complementary
  • Endothelial Cells
  • Endothelium, Vascular
  • Energy Metabolism
  • Expressed Sequence Tags
  • Extracellular Matrix Proteins
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Library
  • Heat-Shock Proteins
  • Humans
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Subtraction Technique
  • Transcription, Genetic

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1152/physiolgenomics.00221.2003

PubMed ID

  • 15100389

Additional Document Info

start page

  • 70

end page

  • 78

volume

  • 18

number

  • 1