Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation

Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:1

Enthalten in:

Nature cardiovascular research - 1(2022), 12 vom: 30. Dez., Seite 1140-1155

Sprache:

Englisch

Beteiligte Personen:

Mokry, Michal [VerfasserIn]
Boltjes, Arjan [VerfasserIn]
Slenders, Lotte [VerfasserIn]
Bel-Bordes, Gemma [VerfasserIn]
Cui, Kai [VerfasserIn]
Brouwer, Eli [VerfasserIn]
Mekke, Joost M [VerfasserIn]
Depuydt, Marie A C [VerfasserIn]
Timmerman, Nathalie [VerfasserIn]
Waissi, Farahnaz [VerfasserIn]
Verwer, Maarten C [VerfasserIn]
Turner, Adam W [VerfasserIn]
Khan, Mohammad Daud [VerfasserIn]
Hodonsky, Chani J [VerfasserIn]
Benavente, Ernest Diez [VerfasserIn]
Hartman, Robin J G [VerfasserIn]
van den Dungen, Noortje A M [VerfasserIn]
Lansu, Nico [VerfasserIn]
Nagyova, Emilia [VerfasserIn]
Prange, Koen H M [VerfasserIn]
Kovacic, Jason C [VerfasserIn]
Björkegren, Johan L M [VerfasserIn]
Pavlos, Eleftherios [VerfasserIn]
Andreakos, Evangelos [VerfasserIn]
Schunkert, Heribert [VerfasserIn]
Owens, Gary K [VerfasserIn]
Monaco, Claudia [VerfasserIn]
Finn, Aloke V [VerfasserIn]
Virmani, Renu [VerfasserIn]
Leeper, Nicholas J [VerfasserIn]
de Winther, Menno P J [VerfasserIn]
Kuiper, Johan [VerfasserIn]
de Borst, Gert J [VerfasserIn]
Stroes, Erik S G [VerfasserIn]
Civelek, Mete [VerfasserIn]
de Kleijn, Dominique P V [VerfasserIn]
den Ruijter, Hester M [VerfasserIn]
Asselbergs, Folkert W [VerfasserIn]
van der Laan, Sander W [VerfasserIn]
Miller, Clint L [VerfasserIn]
Pasterkamp, Gerard [VerfasserIn]

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Anmerkungen:

Date Revised 04.11.2023

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1038/s44161-022-00171-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36412721X