Figure 5.

Transcriptomic profiling of mouse aortic root atherosclerotic plaque shows increased unfolded protein response (UPR) in modulated vascular smooth muscle cells (SMCs). A, t-stochastic neighbor embedding (t-SNE) representation of various cell clusters detected in mouse aortic roots at baseline, and after 8 and 16 wk of high-fat diet (HFD) feeding. The disease-specific modulated SMC cluster, as identified by Wirka et al,¹⁷ is highlighted by the dotted red circle. B–E, t-SNE visualization of cell clusters at the 3 time points overlaid with expression of various genes shows decreased expression of the contractile marker Acta2 (B) and increased expression of the macrophage marker Lgals3 (C), the UPR effector Atf4 (D), and Klf4 (E), which is known to be responsible for phenotypic switching, in the modulated SMC cluster that appears over time on HFD. The scale on the right of each gene indicates level of expression. Analysis was performed on published single-cell RNA sequencing data (GSE131780) from Wirka et al¹⁷ where n=3 mice were used at each time point. Lgals3 indicates lectin, galactoside-binding, soluble, 3.