Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization

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Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization

Karlöf, Eva (author): Karolinska Institutet

Seime, Till (author): Karolinska Institutet

Dias, Nuno (author): Skane Univ Hosp, Dept Vasc Surg, Vasc Ctr, Malmo, Sweden.

Lengquist, Mariette (author): Karolinska Institutet

Witasp, Anna (author): Karolinska Institutet

Almqvist, Hakan (author): Karolinska Institutet

Kronqvist, Malin (author): Karolinska Institutet

Gadin, Jesper R. (author): Karolinska Institutet

Odeberg, Jacob, Professor, 1963- (author): Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap

Maegdefessel, Lars (author): Karolinska Institutet

Stenvinkel, Peter (author): Karolinska Institutet

Matic, Ljubica Perisic (author): Karolinska Institutet

Hedin, Ulf (author): Karolinska Institutet

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Karolinska Institutet Skane Univ Hosp, Dept Vasc Surg, Vasc Ctr, Malmo, Sweden (creator_code:org_t)

ISSN 0021-9150
Stockholm : ELSEVIER IRELAND LTD, 2019
2019
English.
In: Atherosclerosis. - Stockholm : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 288, s. 175-185

Related links:: https://doi.org/10.1...; show more...; http://www.atheroscl...; http://hdl.handle.ne... (primary) (Object in context) (free); https://urn.kb.se/re...; https://doi.org/10.1...; http://hdl.handle.ne...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Background and aims: Unstable carotid atherosclerosis causes stroke, but methods to identify patients and lesions at risk are lacking. We recently found enrichment of genes associated with calcification in carotid plaques from asymptomatic patients. Here, we hypothesized that calcification represents a stabilising feature of plaques and investigated how macro-calcification, as estimated by computed tomography (CT), correlates with gene expression profiles in lesions. Methods: Plaque calcification was measured in pre-operative CT angiographies. Plaques were sorted into high- and low-calcified, profiled with microarrays, followed by bioinformatic analyses. Immunohistochemistry and qPCR were performed to evaluate the findings in plaques and arteries with medial calcification from chronic kidney disease patients. Results: Smooth muscle cell (SMC) markers were upregulated in high-calcified plaques and calcified plaques from symptomatic patients, whereas macrophage markers were downregulated. The most enriched processes in high-calcified plaques were related to SMCs and extracellular matrix (ECM) organization, while inflammation, lipid transport and chemokine signaling were repressed. These findings were confirmed in arteries with high medial calcification. Proteoglycan 4 (PRG4) was identified as the most upregulated gene in association with plaque calcification and found in the ECM, SMA+ and CD68+/TRAP + cells. Conclusions: Macro-calcification in carotid lesions correlated with a transcriptional profile typical for stable plaques, with altered SMC phenotype and ECM composition and repressed inflammation. PRG4, previously not described in atherosclerosis, was enriched in the calcified ECM and localized to activated macrophages and smooth muscle-like cells. This study strengthens the notion that assessment of calcification may aid evaluation of plaque phenotype and stroke risk.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)

Keyword

Atherosclerosis
Computed tomography
Microarrays
Calcification
Carotid stenosis
Smooth muscle cells

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art (subject category)

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By the author/editor: Karlöf, Eva; Seime, Till; Dias, Nuno; Lengquist, Marie ...; Witasp, Anna; Almqvist, Hakan; show more...; Kronqvist, Malin; Gadin, Jesper R.; Odeberg, Jacob, ...; Maegdefessel, La ...; Stenvinkel, Pete ...; Matic, Ljubica P ...; Hedin, Ulf; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

Articles in the publication: Atherosclerosis

By the university: Royal Institute of Technology; Karolinska Institutet

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