TY  - JOUR
A1  - Albarrán Juárez, Julián Alberto
A1  - Kaur, Harmandeep
A1  - Grimm, Myriam Carola
A1  - Offermanns, Stefan
A1  - Wettschureck, Nina
T1  - Lineage tracing of cells involved in atherosclerosis
T2  - Atherosclerosis
N2  - 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.
KW  - Atherosclerosis
KW  - Lineage tracing
KW  - Gene expression
KW  - Smooth muscle cell
KW  - Macrophage Transdifferentiation
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42274
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-422746
SN  - 0021-9150
SN  - 1879-1484
N1  - © 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 251
SP  - 445
EP  - 453
PB  - Elsevier Science
CY  - Amsterdam [u. a.]
ER  -