TY - JOUR
T1 - Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability
AU - Evrard, Solene M.
AU - Lecce, Laura
AU - Michelis, Katherine C.
AU - Nomura-Kitabayashi, Aya
AU - Pandey, Gaurav
AU - Purushothaman, K. Raman
AU - D'Escamard, Valentina
AU - Li, Jennifer R.
AU - Hadri, Lahouaria
AU - Fujitani, Kenji
AU - Moreno, Pedro R.
AU - Benard, Ludovic
AU - Rimmele, Pauline
AU - Cohain, Ariella
AU - Mecham, Brigham
AU - Randolph, Gwendalyn J.
AU - Nabel, Elizabeth G.
AU - Hajjar, Roger
AU - Fuster, Valentin
AU - Boehm, Manfred
AU - Kovacic, Jason C.
N1 - Funding Information:
J.C.K. and this project were directly supported by National Institutes of Health (NIH) Grant K08HL111330. J.C.K. also acknowledges support from NIH R01HL130423
PY - 2016/6/24
Y1 - 2016/6/24
N2 - 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-β signalling, oxidative stress and hypoxia; all hallmarks of atherosclerosis. â €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.
AB - 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-β signalling, oxidative stress and hypoxia; all hallmarks of atherosclerosis. â €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.
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U2 - 10.1038/ncomms11853
DO - 10.1038/ncomms11853
M3 - Article
C2 - 27340017
AN - SCOPUS:84976349019
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 11853
ER -