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Gene expression sig...
Gene expression signatures, pathways and networks in carotid atherosclerosis
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- Perisic, L. (author)
- Karolinska Institutet
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- Aldi, S. (author)
- Karolinska Institutet
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Sun, Y. (author)
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Folkersen, L. (author)
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- Razuvaev, A. (author)
- Karolinska Institutet
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- Roy, J. (author)
- Karolinska Institutet
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- Lengquist, M. (author)
- Karolinska Institutet
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Akesson, S. (author)
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- Wheelock, C. E. (author)
- Karolinska Institutet
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Maegdefessel, L. (author)
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- Gabrielsen, A. (author)
- Karolinska Institutet
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- Odeberg, Jacob (author)
- Karolinska Institutet,KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Department of Medicine, Karolinska Institute, Stockholm, Sweden
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- Hansson, G. K. (author)
- Karolinska Institutet
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- Paulsson-Berne, G. (author)
- Karolinska Institutet
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- Hedin, U. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2015-11-30
- 2016
- English.
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In: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 279:3, s. 293-308
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Abstract
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- BackgroundEmbolism from unstable atheromas in the carotid bifurcation is a major cause of stroke. Here, we analysed gene expression in endarterectomies from patients with symptomatic (S) and asymptomatic (AS) carotid stenosis to identify pathways linked to plaque instability. MethodsMicroarrays were prepared from plaques (n = 127) and peripheral blood samples (n = 96) of S and AS patients. Gene set enrichment, pathway mapping and network analyses of differentially expressed genes were performed. ResultsThese studies revealed upregulation of haemoglobin metabolism (P = 2.20E-05) and bone resorption (P = 9.63E-04) in S patients. Analysis of subgroups of patients indicated enrichment of calcification and osteoblast differentiation in S patients on statins, as well as inflammation and apoptosis in plaques removed >1 month compared to <2 weeks after symptom. By prediction profiling, a panel of 30 genes, mostly transcription factors, discriminated between plaques from S versus AS patients with 78% accuracy. By meta-analysis, common gene networks associated with atherosclerosis mapped to hypoxia, chemokines, calcification, actin cytoskeleton and extracellular matrix. A set of dysregulated genes (LMOD1, SYNPO2, PLIN2 and PPBP) previously not described in atherosclerosis were identified from microarrays and validated by quantitative PCR and immunohistochemistry. ConclusionsOur findings confirmed a central role for inflammation and proteases in plaque instability, and highlighted haemoglobin metabolism and bone resorption as important pathways. Subgroup analysis suggested prolonged inflammation following the symptoms of plaque instability and calcification as a possible stabilizing mechanism by statins. In addition, transcriptional regulation may play an important role in the determination of plaque phenotype. The results from this study will serve as a basis for further exploration of molecular signatures in carotid atherosclerosis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
Keyword
- atherosclerosis
- carotid plaques
- gene expression
- microarrays
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Perisic, L.
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Aldi, S.
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Sun, Y.
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Folkersen, L.
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Razuvaev, A.
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Roy, J.
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show more...
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Lengquist, M.
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Akesson, S.
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Wheelock, C. E.
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Maegdefessel, L.
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Gabrielsen, A.
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Odeberg, Jacob
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Hansson, G. K.
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Paulsson-Berne, ...
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Hedin, U.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Other Clinical M ...
- Articles in the publication
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Journal of Inter ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet