Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis

BMC Med Genomics. 2011 Feb 28;4:20. doi: 10.1186/1755-8794-4-20.


Background: The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling of the artery after injury by coronary stent implantation. We hypothesized that the analysis of gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences in transcript expression between individuals who develop ISR and those who do not.

Methods and results: We determined and investigated PBMC gene expression of 358 patients undergoing an index procedure to treat in de novo coronary artery lesions with bare metallic stents, using a novel time-varying intercept model to optimally assess the time course of gene expression across a time course of blood samples. Validation analyses were conducted in an independent sample of 97 patients with similar time-course blood sampling and gene expression data. We identified 47 probesets with differential expression, of which 36 were validated upon independent replication testing. The genes identified have varied functions, including some related to cellular growth and metabolism, such as the NAB2 and LAMP genes.

Conclusions: In a study of patients undergoing bare metallic stent implantation, we have identified and replicated differential gene expression in peripheral blood mononuclear cells, studied across a time series of blood samples. The genes identified suggest alterations in cellular growth and metabolism pathways, and these results provide the basis for further specific functional hypothesis generation and testing of the mechanisms of ISR.

Publication types

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

MeSH terms

  • Aged
  • Blood Cells / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Coronary Restenosis / genetics*
  • Coronary Restenosis / metabolism
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Software
  • Stents*
  • Time Factors


  • Cell Adhesion Molecules, Neuronal
  • GPI-Linked Proteins
  • NAB2 protein, human
  • Repressor Proteins
  • limbic system-associated membrane protein