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

Santhi K. Ganesh, Jungnam Joo, Kimberly Skelding, Laxmi Mehta, Gang Zheng, Kathleen O'Neill, Eric M. Billings, Anna Helgadottir, Karl Andersen, Gudmundur Thorgeirsson, Thorarinn Gudnason, Nancy L. Geller, Robert D. Simari, David Holmes, William W. O'Neill, Elizabeth G. Nabel

Research output: Contribution to journalArticle

6 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Article number20
JournalBMC Medical Genomics
Volume4
DOIs
StatePublished - 2011

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Stents
Gene Expression
Genes
Blood Cells
Neointima
Growth
Vascular Diseases
Coronary Vessels
Arteries
Wounds and Injuries

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis. / Ganesh, Santhi K.; Joo, Jungnam; Skelding, Kimberly; Mehta, Laxmi; Zheng, Gang; O'Neill, Kathleen; Billings, Eric M.; Helgadottir, Anna; Andersen, Karl; Thorgeirsson, Gudmundur; Gudnason, Thorarinn; Geller, Nancy L.; Simari, Robert D.; Holmes, David; O'Neill, William W.; Nabel, Elizabeth G.

In: BMC Medical Genomics, Vol. 4, 20, 2011.

Research output: Contribution to journalArticle

Ganesh, SK, Joo, J, Skelding, K, Mehta, L, Zheng, G, O'Neill, K, Billings, EM, Helgadottir, A, Andersen, K, Thorgeirsson, G, Gudnason, T, Geller, NL, Simari, RD, Holmes, D, O'Neill, WW & Nabel, EG 2011, 'Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis', BMC Medical Genomics, vol. 4, 20. https://doi.org/10.1186/1755-8794-4-20
Ganesh, Santhi K. ; Joo, Jungnam ; Skelding, Kimberly ; Mehta, Laxmi ; Zheng, Gang ; O'Neill, Kathleen ; Billings, Eric M. ; Helgadottir, Anna ; Andersen, Karl ; Thorgeirsson, Gudmundur ; Gudnason, Thorarinn ; Geller, Nancy L. ; Simari, Robert D. ; Holmes, David ; O'Neill, William W. ; Nabel, Elizabeth G. / Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis. In: BMC Medical Genomics. 2011 ; Vol. 4.
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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. 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.",
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AU - Ganesh, Santhi K.

AU - Joo, Jungnam

AU - Skelding, Kimberly

AU - Mehta, Laxmi

AU - Zheng, Gang

AU - O'Neill, Kathleen

AU - Billings, Eric M.

AU - Helgadottir, Anna

AU - Andersen, Karl

AU - Thorgeirsson, Gudmundur

AU - Gudnason, Thorarinn

AU - Geller, Nancy L.

AU - Simari, Robert D.

AU - Holmes, David

AU - O'Neill, William W.

AU - Nabel, Elizabeth G.

PY - 2011

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N2 - 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.

AB - 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.

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