Format

Send to

Choose Destination
Nat Commun. 2016 Jun 24;7:11853. doi: 10.1038/ncomms11853.

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

Author information

1
The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
2
Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
3
Trialomics LLC, Seattle, Washington 98115, USA.
4
Department of Pathology and Immunology, Washington University, St Louis, Missouri 63110, USA.
5
Brigham and Women's Health Care, Boston, Massachusetts 02115, USA.
6
Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
7
Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
8
Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.

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.

PMID:
27340017
PMCID:
PMC4931033
DOI:
10.1038/ncomms11853
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center