The current paradigm is that smooth muscle cells (SMCs) can adopt various phenotypes in atherosclerotic lesions, including a pro-inflammatory macrophage-like phenotype that might promote plaque rupture. A new study using single-cell RNA sequencing now shows that rather than assuming multiple phenotypes, SMCs transform almost exclusively into fibroblast-like cells (termed fibromyocytes) in atherosclerotic lesions in vivo in both humans and mice. This fibromyocyte phenotype is promoted by the expression of TCF21, a gene that has been causally associated with coronary artery disease (CAD). SMC-specific Tcf21 deletion in Apoe–/– mice markedly reduced SMC transition to fibromyocytes, leading to thinner fibrous caps. TCF21-expressing fibromyocytes were also present in human atherosclerotic lesions, and lower TCF21 levels in SMCs were associated with a higher risk of CAD. “These data suggest that both TCF21 expression and SMC phenotypic modulation are beneficial during the disease process,” conclude the authors.
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Wirka, R. C. et al. Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis. Nat. Med. https://doi.org/10.1038/s41591-019-0512-5 (2019)
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Fernández-Ruiz, I. SMC switch to fibromyocytes is atheroprotective. Nat Rev Cardiol 16, 578 (2019). https://doi.org/10.1038/s41569-019-0255-5
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DOI: https://doi.org/10.1038/s41569-019-0255-5