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
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
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.
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.