TY - JOUR
T1 - Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation
AU - Mokry, Michal
AU - Boltjes, Arjan
AU - Slenders, Lotte
AU - Bel-Bordes, Gemma
AU - Cui, Kai
AU - Brouwer, Eli
AU - Mekke, Joost M.
AU - Depuydt, Marie A. C.
AU - Timmerman, Nathalie
AU - Waissi, Farahnaz
AU - Verwer, Maarten C.
AU - Turner, Adam W.
AU - Khan, Mohammad Daud
AU - Hodonsky, Chani J.
AU - Diez Benavente, Ernest
AU - Hartman, Robin J. G.
AU - van den Dungen, Noortje A. M.
AU - Lansu, Nico
AU - Nagyova, Emilia
AU - Prange, Koen H. M.
AU - Kovacic, Jason C.
AU - Björkegren, Johan L. M.
AU - Pavlos, Eleftherios
AU - Andreakos, Evangelos
AU - Schunkert, Heribert
AU - Owens, Gary K.
AU - Monaco, Claudia
AU - Finn, Aloke V.
AU - Virmani, Renu
AU - Leeper, Nicholas J.
AU - de Winther, Menno P. J.
AU - Kuiper, Johan
AU - de Borst, Gert J.
AU - Stroes, Erik S. G.
AU - Civelek, Mete
AU - de Kleijn, Dominique P. V.
AU - den Ruijter, Hester M.
AU - Asselbergs, Folkert W.
AU - van der Laan, Sander W.
AU - Miller, Clint L.
AU - Pasterkamp, Gerard
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved subphenotyping. Here, we analyzed 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. Furthermore, we did a preliminary analysis of potential circulating biomarkers that mark the different plaque 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.
AB - Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved subphenotyping. Here, we analyzed 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. Furthermore, we did a preliminary analysis of potential circulating biomarkers that mark the different plaque 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85164137676&origin=inward
U2 - https://doi.org/10.1038/s44161-022-00171-0
DO - https://doi.org/10.1038/s44161-022-00171-0
M3 - Article
C2 - 37920851
SN - 2731-0590
VL - 1
SP - 1140
EP - 1155
JO - Nature cardiovascular research
JF - Nature cardiovascular research
IS - 12
ER -