Lineage tracing of cells involved in atherosclerosis
Open accessAbstract
BACKGROUND AND AIMS: Despite the clinical importance of atherosclerosis, the origin of cells within atherosclerotic plaques is not fully understood. Due to the lack of a definitive lineage-tracing strategy, previous studies have provided controversial results about the origin of cells expressing smooth muscle and macrophage markers in atherosclerosis. We here aim to identify the origin of vascular smooth muscle (SM) cells and macrophages within atherosclerosis lesions. METHODS: We combined a genetic fate mapping approach with single cell expression analysis in a murine model of atherosclerosis. RESULTS: We found that 16% of CD68-positive plaque macrophage-like cells were derived from mature SM cells and not from myeloid sources, whereas 31% of αSMA-positive smooth muscle-like cells in plaques were not SM-derived. Further analysis at the single cell level showed that SM-derived CD68(+) cells expressed higher levels of inflammatory markers such as cyclooxygenase 2 (Ptgs2, p = 0.02), and vascular cell adhesion molecule (Vcam1, p = 0.05), as well as increased mRNA levels of genes related to matrix synthesis such as Col1a2 (p = 0.01) and Fn1 (p = 0.04), than non SM-derived CD68(+) cells. CONCLUSIONS: These results demonstrate that smooth muscle cells within atherosclerotic lesions can switch to a macrophage-like phenotype characterized by higher expression of inflammatory and synthetic markers genes that may further contribute to plaque progression.
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Lineage tracing studies have unambiguously demonstrated that VSMCs contribute substantially to plaque formation in murine models of atherosclerosis, generating 30-70% of all plaque cells.
“Lineage tracing studies have unambiguously demonstrated that VSMCs contribute substantially to plaque formation in murine models of atherosclerosis, generating 30-70% of all plaque cells 11,18-20,22,23 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [19]
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- Authors
- Albarrán-Juárez, J., Kaur, H., Grimm, M., Offermanns, S., & Wettschureck, N.
- Affiliations
- Max Planck Institute for Heart and Lung Research (DE)
- Goethe University Frankfurt (DE)
- Corresponding author
- Albarrán-Juárez, Julián
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 251
- Pages
- 445-453
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W2414168448
- Cited by
- 90
- References
- 28
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 10 · 2023: 3 · 2022: 8 · 2021: 15 · 2020: 8 · 2019: 9 · 2018: 7 · 2017: 10 · 2016: 3
- FWCI
- 5.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Atherosclerosis (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- German Research Foundation (Project C7)
- 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, plaque macrophages, lineage tracing, fate mapping, inflammation, extracellular matrix genes, atherosclerotic plaque progression
- MeSH terms
- CD68 Molecule, Animals, Chromosome Mapping, Gene Expression Regulation, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular, Phenotype, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Cell Lineage, Myeloid Cells, Myocytes, Smooth Muscle, Atherosclerosis, Mice
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