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Molecular Phenotypes of Coronary Artery Disease: The Stockholm Atherosclerosis Gene Expression (STAGE) Study
Linköping University, Department of Physics, Chemistry and Biology, Computational Biology. Linköping University, The Institute of Technology.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]


By offering a comprehensive view of the molecular underpinnings of pathology, high-dimensional data have the potential to revolutionize the diagnosis and management of complex disorders such as coronary artery disease (CAD). To identify molecular phenotypes of CAD, we performed multi organ gene expression profiling of subjects enrolled in the Stockholm Atherosclerosis Gene Expression (STAGE) study.


Atherosclerotic and unaffected arterial wall, liver, skeletal muscle, and mediastinal fat biopsies were obtained during coronary artery bypass grafting from 114 well-characterized CAD patients. RNA samples were isolated, and 278 transcription profiles were obtained using Affymetrix HG-U133_Plus_2 GeneChips.


The most prominent molecular phenotype of the CAD patients was represented by 733 genes in mediastinal fat, which were involved in extracellular matrix organization, response to stress and regulation of programmed cell death. Other aspects of this phenotype were shared with liver (e.g., oxidoreductase activity), skeletal muscle (insulin-like growth factor binding), and atherosclerotic arterial wall (cell motility and adhesion, fatty acid metabolism). In addition, the activity of 400 genes exclusively in mediastinal fat was associated with the extent of coronary stenosis and atherosclerosis. Immune-cell activation in mediastinal fat defined CAD patients with poor blood glucose control and prolonged hospitalization.


The molecular phenotype of mediastinal fat appears to be central in CAD and should be useful for early identification of CAD risk.

National Category
Natural Sciences
URN: urn:nbn:se:liu:diva-102663OAI: diva2:680728
Available from: 2013-12-18 Created: 2013-12-18 Last updated: 2013-12-18
In thesis
1. Gene Expression Profiling of Human Atherosclerosis
Open this publication in new window or tab >>Gene Expression Profiling of Human Atherosclerosis
2006 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Atherosclerosis is the main underlying cause of coronary artery disease (CAD) and stroke. These two diseases are leading causes of death in the developed world. The socio-economical cost for treatments and absence of work is enormous. Recent numbers from the US show no tendency of decline in the spread of atherosclerosis.

Common risk factors for premature atherosclerosis are obesity, diabetes, smoking, physical inactivity and high blood pressure. Medications have been developed for treatment of risk factors and a breakthrough was the release of statins, an effective lipid-lowering drug. Nevertheless, atherosclerosis is multi-factorial and all the different players in the pathological process are not yet identified. New large-scale studies, such as gene expression profiling, are needed to understand the interplay between risk factors and pathways in atherosclerosis and with that reveal new therapeutic targets.

In this thesis two studies are presented where gene expression profiling in well-characterized patients suffering from severe atherosclerosis have been performed. In study number one, five types of tissues (atherosclerotic aortic root, unatherosclerotic mammary artery, mediastinal fat, skeletal muscle and liver) were collected from a total of 66 patients undergoing coronary by-pass surgery. Subjects were also screened for cardiovascular risk factors. RNA was isolated from the biopsies and gene expression analysis using Affymetrix GeneChip system was performed. The main result showed that mediastinal fat appears to be central in CAD.

In study number two, gene expression analysis of plaques from patients undergoing carotid endorectomy was performed. Again, all patients were screened for conventional risk factors and RNA was isolated and expression profiles were obtained using Affymetrix technology. Cluster analyses identified genes associated to intima-media thickness in these patients.

Taken together, expression analyses of clinical whole-genome expression datasets can be used to identify novel pathways and individual genes with possible importance for atherosclerosis development.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2006. 29 p.
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1279
National Category
Natural Sciences
urn:nbn:se:liu:diva-36166 (URN)30277 (Local ID)91-85643-62-9 (ISBN)30277 (Archive number)30277 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2013-12-18

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