Cited by 578Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismCerebrovascular and Carotid Artery Diseases

Transdifferentiation of Vascular Smooth Muscle Cells to Macrophage-Like Cells During Atherogenesis

Feil, Susanne, Fehrenbacher, Birgit, Lukowski, Robert, Essmann, Frank, Schulze-Osthoff, Klaus, Schaller, Martin, Feil, Robert·2014·Circulation Research

Abstract

Rationale: Atherosclerosis is a widespread and devastating disease, but the origins of cells within atherosclerotic plaques are not well defined. Objective: To investigate the specific contribution of vascular smooth muscle cells (SMCs) to atherosclerotic plaque formation by genetic inducible fate mapping in mice. Methods and Results: Vascular SMCs were genetically pulse-labeled using the tamoxifen-dependent Cre recombinase, CreER T2 , expressed from the endogenous SM22α locus combined with Cre-activatable reporter genes that were integrated into the ROSA26 locus. Mature SMCs in the arterial media were labeled by tamoxifen treatment of young apolipoprotein E–deficient mice before the development of atherosclerosis and then their fate was monitored in older atherosclerotic animals. We found that medial SMCs can undergo clonal expansion and convert to macrophage-like cells that have lost classic SMC marker expression and make up a major component of advanced atherosclerotic lesions. Conclusions: This study provides strong in vivo evidence for smooth muscle-to-macrophage transdifferentiation and supports an important role of SMC plasticity in atherogenesis. Targeting this type of SMC phenotypic conversion might be a novel strategy for the treatment of atherosclerosis, as well as other diseases with a smooth muscle component.

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Registry

Crossref · 10.1161/circresaha.115.304634

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31 of 31 references verified0 citation errors · 0 not checkable

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  • Some plaque reporter-expressing cells were positive for Mac-3, Lgals3 and CD68, markers previously used to study macrophages in atherosclerosis.

    “Instead, some plaque reporter-expressing cells were positive for Mac-3 20 , Lgals3 11 and CD68 17 - markers that have been previously used to study macrophages in atherosclerosis.”

    From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [17]

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Authors
Feil, S., Fehrenbacher, B., Lukowski, R., Essmann, F., Schulze-Osthoff, K., Schaller, M., & Feil, R.
Affiliations
  • University of Tübingen (DE)
  • From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany.
Venue
Circulation Research
Published
2014-09-12
Volume
115
Issue
7
Pages
662-667
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2141814949
Cited by
578
References
31
Citations by year
2026: 33 · 2025: 52 · 2024: 63 · 2023: 57 · 2022: 56 · 2021: 59 · 2020: 46 · 2019: 39 · 2018: 42 · 2017: 48 · 2016: 42 · 2015: 33 · 2014: 6
FWCI
19.63
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Volkswagen Foundation
  • Medizinischen Fakultät, Eberhard Karls Universität Tübingen
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
Keywords
vascular smooth muscle cells, transdifferentiation, macrophage-like cells, atherogenesis, atherosclerosis, clonal expansion, atherosclerotic plaque, SM22α, Rosa26 reporter, ApoE-deficient mice, cell fate mapping
MeSH terms
Animals, Apolipoproteins E, Macrophages, Microfilament Proteins, Muscle Proteins, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Mice, Cell Transdifferentiation, Plaque, Atherosclerotic

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