2026-05-20T23:01:12Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/99552024-09-27T08:31:32Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Jacobsen, Kevin
author
Lund, Marie Bek
author
Shim, Jeong T
author
Gunnersen, Stine
author
Füchtbauer, Ernst-Martin
author
Kjolby, Mads
author
Carramolino, Laura
author
Bentzon, Jacob F
funder
Danish Independent Research Council
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación ProCNIC
2020-05-07T14:34:50Z
2020-05-07T14:34:50Z
2017-10
JCI Insight. 2017; 2(19):95890
10.1172/jci.insight.95890
2379-3708
2379-3708
JCI insight
28978793
http://hdl.handle.net/20.500.12105/9955
Fibrous cap smooth muscle cells (SMCs) protect atherosclerotic lesions from rupturing and causing thrombosis, while other plaque SMCs may have detrimental roles in plaque development. To gain insight into recruitment of different plaque SMCs, we mapped their clonal architecture in aggregation chimeras of eGFP+Apoe-/- and Apoe-/- mouse embryos and in mice with a mosaic expression of fluorescent proteins in medial SMCs that were rendered atherosclerotic by PCSK9-induced hypercholesterolemia. Fibrous caps in aggregation chimeras were found constructed from large, endothelial-aligned layers of either eGFP+ or nonfluorescent SMCs, indicating substantial clonal expansion of a few cells. Similarly, plaques in mice with SMC-restricted Confetti expression showed oligoclonal SMC populations with little intermixing between the progeny of different medial SMCs. Phenotypes comprised both ACTA2+ SMCs in the cap and heterogeneous ACTA2- SMCs in the plaque interior, including chondrocyte-like cells and cells with intracellular lipid and crystalline material. Fibrous cap SMCs were invariably arranged in endothelium-aligned clonal sheets, confirming results in the aggregation chimeras. Analysis of the clonal structure showed that a low number of local medial SMCs partake in atherosclerosis and that single medial SMCs can produce several different SMC phenotypes in plaque. The combined results show that few medial SMCs proliferate to form the entire phenotypically heterogeneous plaque SMC population in murine atherosclerosis.
eng
Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs
journal article
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DiverseCellularArchitectureAtherosclerotic_2017.pdf
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https://repisalud.isciii.es/bitstreams/87083bd7-602b-41ae-9dbe-d0f52a8d4796/download
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DiverseCellularArchitectureAtherosclerotic_2017.pdf.txt