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Differential gene expression in coronary arteries from patients presenting with ischemic heart disease: Further evidence for the inflammatory basis of atherosclerosis

The pathogenesis of human coronary artery disease (CAD) is likely to require the transcription of many different genes. We report here the differential gene expression profiling of human CAD using copy DNA (cDNA)/nylon array hybridization techniques. Human coronary arteries were obtained at the time... Full description

Journal Title: The American heart journal 2005, Vol.150 (3), p.488-499
Main Author: Satterthwaite, Gemma
Other Authors: Francis, Sheila E , Suvarna, Kim , Blakemore, Stephen , Ward, Chantelle , Wallace, Don , Braddock, Martin , Crossman, David
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: New York, NY: Mosby, Inc
ID: ISSN: 0002-8703
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title: Differential gene expression in coronary arteries from patients presenting with ischemic heart disease: Further evidence for the inflammatory basis of atherosclerosis
format: Article
creator:
  • Satterthwaite, Gemma
  • Francis, Sheila E
  • Suvarna, Kim
  • Blakemore, Stephen
  • Ward, Chantelle
  • Wallace, Don
  • Braddock, Martin
  • Crossman, David
subjects:
  • Abridged Index Medicus
  • Analysis
  • Apoptosis
  • Arrays
  • Atherosclerosis
  • Atherosclerosis (general aspects, experimental research)
  • Biological and medical sciences
  • Blood and lymphatic vessels
  • Cardiac patients
  • Cardiology. Vascular system
  • Cardiovascular disease
  • Cloning
  • Cluster Analysis
  • Coronary arteries
  • Coronary Artery Disease - genetics
  • Coronary Artery Disease - immunology
  • Coronary heart disease
  • Coronary Vessels - chemistry
  • Cytokines
  • Data analysis
  • Endothelium
  • Gene expression
  • Gene Expression Regulation
  • Genetic aspects
  • Genetic engineering
  • Genetic research
  • Heart
  • Humans
  • Inflammation
  • Ischemia
  • Kinases
  • Medical sciences
  • Myocardial ischemia
  • Myocardial Ischemia - genetics
  • Myocardial Ischemia - immunology
  • Myocarditis. Cardiomyopathies
  • Nylon
  • Oligonucleotide Array Sequence Analysis
  • Patients
  • STAT6 Transcription Factor - analysis
  • STAT6 Transcription Factor - genetics
  • Studies
ispartof: The American heart journal, 2005, Vol.150 (3), p.488-499
description: The pathogenesis of human coronary artery disease (CAD) is likely to require the transcription of many different genes. We report here the differential gene expression profiling of human CAD using copy DNA (cDNA)/nylon array hybridization techniques. Human coronary arteries were obtained at the time of cardiac transplantation. Ten patients were transplanted for ischemic heart disease (IHD) and 5 for dilated cardiomyopathy (DCM). We generated a customized cDNA array containing 9206 clones and after hybridization of patient samples, data reduction, and refinement, identified 515 sequence-verified, differentially expressed clones. These clones represented 361 genes that were differentially expressed at significant levels between IHD and DCM arteries ( t test, P < .05). Of these clones, 70% were defined genes of known function and 30% were genes of unknown function. Of the differentially expressed genes, 53.6% were up-regulated and 46.4% were down-regulated. Hierarchical clustering was performed and several distinct functional clusters were identified, including a cluster of genes related to inflammatory mechanisms. Validation by real-time polymerase chain reaction was undertaken with 2 genes known to be up-regulated in atherosclerosis (interleukin 1β [IL-1β] and IL-8) and 2 novel genes identified by the array analysis (signal transducer and activator of transcription 6 [STAT6] and IL-1 receptor–associated kinase [IRAK]). Differential expression of IL-1β, IL-8, and STAT6 were confirmed by this method. Immunohistochemistry of STAT6 demonstrated increased expression in vascular smooth muscle cells of IHD coronary arteries. These data support the inflammatory basis of human atherosclerotic CAD and identify novel genes in atherosclerosis.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0002-8703
fulltext: fulltext
issn:
  • 0002-8703
  • 1097-6744
url: Link


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descriptionThe pathogenesis of human coronary artery disease (CAD) is likely to require the transcription of many different genes. We report here the differential gene expression profiling of human CAD using copy DNA (cDNA)/nylon array hybridization techniques. Human coronary arteries were obtained at the time of cardiac transplantation. Ten patients were transplanted for ischemic heart disease (IHD) and 5 for dilated cardiomyopathy (DCM). We generated a customized cDNA array containing 9206 clones and after hybridization of patient samples, data reduction, and refinement, identified 515 sequence-verified, differentially expressed clones. These clones represented 361 genes that were differentially expressed at significant levels between IHD and DCM arteries ( t test, P < .05). Of these clones, 70% were defined genes of known function and 30% were genes of unknown function. Of the differentially expressed genes, 53.6% were up-regulated and 46.4% were down-regulated. Hierarchical clustering was performed and several distinct functional clusters were identified, including a cluster of genes related to inflammatory mechanisms. Validation by real-time polymerase chain reaction was undertaken with 2 genes known to be up-regulated in atherosclerosis (interleukin 1β [IL-1β] and IL-8) and 2 novel genes identified by the array analysis (signal transducer and activator of transcription 6 [STAT6] and IL-1 receptor–associated kinase [IRAK]). Differential expression of IL-1β, IL-8, and STAT6 were confirmed by this method. Immunohistochemistry of STAT6 demonstrated increased expression in vascular smooth muscle cells of IHD coronary arteries. These data support the inflammatory basis of human atherosclerotic CAD and identify novel genes in atherosclerosis.
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subjectAbridged Index Medicus ; Analysis ; Apoptosis ; Arrays ; Atherosclerosis ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiac patients ; Cardiology. Vascular system ; Cardiovascular disease ; Cloning ; Cluster Analysis ; Coronary arteries ; Coronary Artery Disease - genetics ; Coronary Artery Disease - immunology ; Coronary heart disease ; Coronary Vessels - chemistry ; Cytokines ; Data analysis ; Endothelium ; Gene expression ; Gene Expression Regulation ; Genetic aspects ; Genetic engineering ; Genetic research ; Heart ; Humans ; Inflammation ; Ischemia ; Kinases ; Medical sciences ; Myocardial ischemia ; Myocardial Ischemia - genetics ; Myocardial Ischemia - immunology ; Myocarditis. Cardiomyopathies ; Nylon ; Oligonucleotide Array Sequence Analysis ; Patients ; STAT6 Transcription Factor - analysis ; STAT6 Transcription Factor - genetics ; Studies
ispartofThe American heart journal, 2005, Vol.150 (3), p.488-499
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1Francis, Sheila E
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3Blakemore, Stephen
4Ward, Chantelle
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6Braddock, Martin
7Crossman, David
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descriptionThe pathogenesis of human coronary artery disease (CAD) is likely to require the transcription of many different genes. We report here the differential gene expression profiling of human CAD using copy DNA (cDNA)/nylon array hybridization techniques. Human coronary arteries were obtained at the time of cardiac transplantation. Ten patients were transplanted for ischemic heart disease (IHD) and 5 for dilated cardiomyopathy (DCM). We generated a customized cDNA array containing 9206 clones and after hybridization of patient samples, data reduction, and refinement, identified 515 sequence-verified, differentially expressed clones. These clones represented 361 genes that were differentially expressed at significant levels between IHD and DCM arteries ( t test, P < .05). Of these clones, 70% were defined genes of known function and 30% were genes of unknown function. Of the differentially expressed genes, 53.6% were up-regulated and 46.4% were down-regulated. Hierarchical clustering was performed and several distinct functional clusters were identified, including a cluster of genes related to inflammatory mechanisms. Validation by real-time polymerase chain reaction was undertaken with 2 genes known to be up-regulated in atherosclerosis (interleukin 1β [IL-1β] and IL-8) and 2 novel genes identified by the array analysis (signal transducer and activator of transcription 6 [STAT6] and IL-1 receptor–associated kinase [IRAK]). Differential expression of IL-1β, IL-8, and STAT6 were confirmed by this method. Immunohistochemistry of STAT6 demonstrated increased expression in vascular smooth muscle cells of IHD coronary arteries. These data support the inflammatory basis of human atherosclerotic CAD and identify novel genes in atherosclerosis.
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abstractThe pathogenesis of human coronary artery disease (CAD) is likely to require the transcription of many different genes. We report here the differential gene expression profiling of human CAD using copy DNA (cDNA)/nylon array hybridization techniques. Human coronary arteries were obtained at the time of cardiac transplantation. Ten patients were transplanted for ischemic heart disease (IHD) and 5 for dilated cardiomyopathy (DCM). We generated a customized cDNA array containing 9206 clones and after hybridization of patient samples, data reduction, and refinement, identified 515 sequence-verified, differentially expressed clones. These clones represented 361 genes that were differentially expressed at significant levels between IHD and DCM arteries ( t test, P < .05). Of these clones, 70% were defined genes of known function and 30% were genes of unknown function. Of the differentially expressed genes, 53.6% were up-regulated and 46.4% were down-regulated. Hierarchical clustering was performed and several distinct functional clusters were identified, including a cluster of genes related to inflammatory mechanisms. Validation by real-time polymerase chain reaction was undertaken with 2 genes known to be up-regulated in atherosclerosis (interleukin 1β [IL-1β] and IL-8) and 2 novel genes identified by the array analysis (signal transducer and activator of transcription 6 [STAT6] and IL-1 receptor–associated kinase [IRAK]). Differential expression of IL-1β, IL-8, and STAT6 were confirmed by this method. Immunohistochemistry of STAT6 demonstrated increased expression in vascular smooth muscle cells of IHD coronary arteries. These data support the inflammatory basis of human atherosclerotic CAD and identify novel genes in atherosclerosis.
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pmid16169330
doi10.1016/j.ahj.2004.10.025