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Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization
Karolinska Univ Hosp, Dept Vasc Surg, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
Skane Univ Hosp, Dept Vasc Surg, Vasc Ctr, Malmo, Sweden..
Karolinska Inst, Dept Mol Med & Surg, L8 03, SE-17176 Stockholm, Sweden..
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2019 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 288, p. 175-185Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD , 2019. Vol. 288, p. 175-185
Keywords [en]
Atherosclerosis, Computed tomography, Microarrays, Calcification, Carotid stenosis, Smooth muscle cells
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:kth:diva-261036DOI: 10.1016/j.atherosclerosis.2019.05.005ISI: 000485127200025PubMedID: 31109707Scopus ID: 2-s2.0-85065760427OAI: oai:DiVA.org:kth-261036DiVA, id: diva2:1356722
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QC 20191002

Available from: 2019-10-02 Created: 2019-10-02 Last updated: 2019-10-02Bibliographically approved

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