title: Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis.
abstract: 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.
  
  
  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.
authors.affiliation: National Heart, Lung, and Blood Institute (NHLBI), Division of Intramural Research, Bethesda, Maryland, USA.
authors.forename: Santhi K
authors.initials: SK
authors.lastname: Ganesh
authors.forename: Jungnam
authors.initials: J
authors.lastname: Joo
authors.forename: Kimberly
authors.initials: K
authors.lastname: Skelding
authors.forename: Laxmi
authors.initials: L
authors.lastname: Mehta
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Neill
authors.forename: Eric M
authors.initials: EM
authors.lastname: Billings
authors.forename: Anna
authors.initials: A
authors.lastname: Helgadottir
authors.forename: Karl
authors.initials: K
authors.lastname: Andersen
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Gudnason
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Geller
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
authors.forename: David R
authors.initials: DR
authors.lastname: Holmes
authors.forename: William W
authors.initials: WW
authors.lastname: O'Neill
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Nabel
mesh_terms: D000368:Aged; D001773:Blood Cells / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D023903:Coronary Restenosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012984:Software; D015607:Stents; D013997:Time Factors
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C491000:NAB2 protein, human; D012097:Repressor Proteins; C095362:limbic system-associated membrane protein