Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability

Solene M. Evrard, Laura Lecce, Katherine C. Michelis, Aya Nomura-Kitabayashi, Gaurav Pandey, K-Raman Purushothaman, Valentina d’Escamard, Jennifer R. Li, Lahouaria Hadri, Kenji Fujitani, Pedro R. Moreno, Ludovic Benard, Pauline Rimmele, Ariella Cohain, Brigham Mecham, Gwendalyn J. Randolph, Elizabeth G. Nabel, Roger Hajjar, Valentin Fuster, Manfred Boehm and Jason C. Kovacic ()
Additional contact information
Solene M. Evrard: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Laura Lecce: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Katherine C. Michelis: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Aya Nomura-Kitabayashi: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Gaurav Pandey: Icahn School of Medicine at Mount Sinai
K-Raman Purushothaman: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Valentina d’Escamard: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Jennifer R. Li: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Lahouaria Hadri: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Kenji Fujitani: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Pedro R. Moreno: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Ludovic Benard: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Pauline Rimmele: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Ariella Cohain: Icahn School of Medicine at Mount Sinai
Brigham Mecham: Trialomics LLC
Gwendalyn J. Randolph: Washington University
Elizabeth G. Nabel: Brigham and Women’s Health Care
Roger Hajjar: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Valentin Fuster: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
Manfred Boehm: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health
Jason C. Kovacic: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract 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. ‘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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11853

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DOI: 10.1038/ncomms11853

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