Lineage tracing of cells involved in atherosclerosis

  • 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.

Download full text files

Export metadata

Author:Julián Alberto Albarrán JuárezORCiDGND, Harmandeep Kaur, Myriam Carola GrimmGND, Stefan OffermannsORCiDGND, Nina WettschureckORCiDGND
Pubmed Id:
Parent Title (English):Atherosclerosis
Publisher:Elsevier Science
Place of publication:Amsterdam [u. a.]
Document Type:Article
Date of Publication (online):2016/11/28
Date of first Publication:2016/06/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/11/28
Tag:Atherosclerosis; Gene expression; Lineage tracing; Macrophage Transdifferentiation; Smooth muscle cell
Page Number:9
First Page:445
Last Page:453
© 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0