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Profiling of athero...
Profiling of atherosclerotic lesions by gene and tissue microarrays reveals pcsk6 as a novel protease in unstable carotid atherosclerosis
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- Perisic, L. (författare)
- Karolinska Institutet
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Hedin, E. (författare)
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- Razuvaev, A. (författare)
- Karolinska Institutet
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- Lengquist, M. (författare)
- Karolinska Institutet
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- Österholm, C. (författare)
- Karolinska Institutet
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Folkersen, L. (författare)
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- Gillgren, P. (författare)
- Karolinska Institutet
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Paulsson-Berne, G. (författare)
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- Pontén, Fredrik (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
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- Odeberg, Jacob (författare)
- KTH,Proteomik och nanobioteknologi
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- Hedin, U. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2013
- 2013
- Engelska.
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 33:10, s. 2432-2443
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- OBJECTIVE - : Carotid plaque instability is a major cause of ischemic stroke, but detailed knowledge about underlying molecular pathways is still lacking. Here, we evaluated large-scale transcriptomic and protein expression profiling in a biobank of carotid endarterectomies followed by characterization of identified candidates, as a platform for discovery of novel proteins differentially regulated in unstable carotid lesions. APPROACH AND RESULTS - : Genes highly upregulated in symptomatic versus asymptomatic plaques were selected from Affymetrix microarray analyses (n=127 plaques), and tissue microarrays constructed from 34 lesions were assayed for 21 corresponding proteins by immunohistochemistry. Quantification of stainings demonstrated differential expression of CD36, CD137, and DOCK7 (P<0.05) in unstable versus stable lesions and the most significant upregulation of a proprotein convertase, PCSK6 (P<0.0001). Increased expression of PCSK6 in symptomatic lesions was verified by quantitative real-time polymerase chain reaction (n=233), and the protein was localized to smooth muscle α-actin positive cells and extracellular matrix of the fibrous cap by immunohistochemistry. PCSK6 expression positively correlated to genes associated with inflammation, matrix degradation, and mitogens in microarrays. Stimulation of human carotid smooth muscle cells in vitro with cytokines caused rapid induction of PCSK6 mRNA. CONCLUSIONS - : Using a combination of transcriptomic and tissue microarray profiling, we demonstrate a novel approach to identify proteins differentially expressed in unstable carotid atherosclerosis. The proprotein convertase PCSK6 was detected at increased levels in the fibrous cap of symptomatic carotid plaques, possibly associated with key processes in plaque rupture such as inflammation and extracellular matrix remodeling. Further studies are needed to clarify the role of PCSK6 in atherosclerosis.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- atherosclerosis
- carotid stenosis
- muscle
- smooth
- symptomatic carotid stenosis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Perisic, L.
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Hedin, E.
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Razuvaev, A.
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Lengquist, M.
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Österholm, C.
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Folkersen, L.
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visa fler...
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Gillgren, P.
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Paulsson-Berne, ...
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Pontén, Fredrik
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Odeberg, Jacob
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Hedin, U.
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
- Artiklar i publikationen
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Arteriosclerosis ...
- Av lärosätet
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Kungliga Tekniska Högskolan
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Karolinska Institutet
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Uppsala universitet