Transcriptional profiling of CD133(+) cells in coronary artery disease and effects of exercise on gene expression

Cytotherapy. 2011 Feb;13(2):227-36. doi: 10.3109/14653249.2010.491611.

Abstract

Background aims: Bone marrow (BM)-derived progenitor cells are under investigation for cardiovascular repair but may be altered by disease. Our aim was to identify differences in gene expression in CD133(+) cells of patients with coronary artery disease (CAD) and healthy controls, and determine whether exercise modifies gene expression.

Methods: CD133(+) cells were flow-sorted from 10 CAD patients and four controls, and total RNA was isolated for microarray-based gene expression profiling. Genes that were found to be differentially regulated in patients were analyzed further to investigate whether exercise had any normalizing effect on CD133(+) cells in CAD patients following 3 months of an exercise program.

Results: Improvement in effort tolerance and increases in the number of CD133(+) cells were observed in CAD patients after 3 months of exercise. Gene expression analysis of the CD133(+) cells identified 82 differentially expressed genes (2-fold cut-off, 25% false-discovery rate and % present calls) in patients compared with controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cell cycle, cellular development and signaling, and molecular transport. Following completion of the exercise program, gene expression patterns resembled those of controls in seven of 10 patients.

Conclusions: Alterations in gene expression of BM-derived CD133(+) progenitor cells were found in CAD patients, which in part may be normalized by exercise.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Antigens, CD / analysis*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Carbohydrate Metabolism
  • Cell Cycle
  • Cell Differentiation
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Exercise*
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression*
  • Glycoproteins / analysis*
  • Humans
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Peptides / analysis*
  • RNA / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription, Genetic

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • Membrane Transport Proteins
  • PROM1 protein, human
  • Peptides
  • RNA