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

Satterthwaite, Gemma, Francis, Sheila E., Suvarna, Kim, Blakemore, Stephen, Ward, Chantelle, Wallace, Don, Braddock, Martin and Crossman, David (2005) Differential gene expression in coronary arteries from patients presenting with ischemic heart disease: further evidence for the inflammatory basis of atherosclerosis. American Heart Journal, 150 (3). pp. 488-499. ISSN 0002-8703

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Abstract

Background and Objective: 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. Methods and Results: 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. Conclusion: These data support the inflammatory basis of human atherosclerotic CAD and identify novel genes in atherosclerosis.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit
Depositing User:	Rhiannon Harvey
Date Deposited:	17 May 2011 15:48
Last Modified:	06 Sep 2023 12:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/30720
DOI:	10.1016/j.ahj.2004.10.025

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