2026-04-29T12:23:40Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/52262024-09-27T08:19:28Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Evrard, Solene M.
author
Lecce, Laura
author
Michelis, Katherine C.
author
Nomura-Kitabayashi, Aya
author
Pandey, Gaurav
author
Purushothaman, K-Raman
author
d'Escamard, Valentina
author
Li, Jennifer R.
author
Hadri, Lahouaria
author
Fujitani, Kenji
author
Moreno, Pedro R.
author
Benard, Ludovic
author
Rimmele, Pauline
author
Cohain, Ariella
author
Mecham, Brigham
author
Randolph, Gwendalyn J.
author
Nabel, Elizabeth G.
author
Hajjar, Roger
author
Fuster, Valentin
author
Boehm, Manfred
author
Kovacic, Jason C.
funder
National Institutes of Health (Estados Unidos)
funder
Fondation Leducq
funder
AstraZeneca
funder
IBM
2017-10-30T13:15:45Z
2017-10-30T13:15:45Z
2016
Nat Commun. 2016; 7:11853
10.1038/ncomms11853
2041-1723
Nature Communications
27340017
http://hdl.handle.net/20.500.12105/5226
Endothelial to mesenchymal transition (EndMT) plays a major role during development, and also contributes to several adult cardiovascular diseases. Importantly, mesenchymal cells including fibroblasts are prominent in atherosclerosis, with key functions including regulation of: inflammation, matrix and collagen production, and plaque structural integrity. However, little is known about the origins of atherosclerosis-associated fibroblasts. Here we show using endothelial-specific lineage-tracking that EndMT-derived fibroblast-like cells are common in atherosclerotic lesions, with EndMT-derived cells expressing a range of fibroblast-specific markers. In vitro modelling confirms that EndMT is driven by TGF-beta signalling, oxidative stress and hypoxia; all hallmarks of atherosclerosis. `Transitioning' cells are readily detected in human plaques co-expressing endothelial and fibroblast/mesenchymal proteins, indicative of EndMT. The extent of EndMT correlates with an unstable plaque phenotype, which appears driven by altered collagen-MMP production in EndMT-derived cells. We conclude that EndMT contributes to atherosclerotic patho-biology and is associated with complex plaques that may be related to clinical events.
eng
FIBROBLAST ACTIVATION PROTEIN
AMERICAN-HEART-ASSOCIATION
MARROW-DERIVED CELLS
SMOOTH-MUSCLE-CELLS
IN-VIVO
PULMONARY-HYPERTENSION
CARDIAC FIBROSIS
RENAL FIBROSIS
EXPRESSION
MICE
Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability
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