Figure 3. Treatment of SMC (Myh11-CreER^T2-eYFP) and EC (Cdh5-CreER^T2-eYFP)-lineage tracing Apoe^−/− mice with advanced atherosclerotic lesions with the senolytic drug ABT-263 (100mg/kg/bw) was associated with a marked reduction in the number of SMC within BCA lesions but an increase in EC-derived cells undergoing EndoMT although the latter did not result in increased investment of EC-derived α-SMA+ cells into the fibrous cap.

(A) Experimental design for figures B-E, SMC-lineage tracing Apoe^−/−mice were fed a WD for 18 weeks followed by 100mg/kg/bw ABT-263 treatment on WD for 6 weeks. (B) Representative confocal images of co-staining for eYFP (for detecting SMC), α-SMA⁺, and DAPI in advanced BCA lesions from experiment A. The confocal images show a maximum intensity projection ×20 zoom and a scale bar of 100μm. (C) α-SMA⁺ cap area normalized to lesion area (α-SMA⁺ cap area/Lesion area). (D) Quantification of the percentage of SMC-derived (Myh11-eYFP⁺/DAPI⁺) cells in the fibrous cap, and (E) quantification of the % SMC-derived α-SMA⁺ (Myh11-eYFP⁺ α-SMA⁺/α-SMA⁺) cells in the fibrous cap. (F) The experimental design for figures H-J, EC-lineage tracing Apoe^−/− mice were fed a WD for 18 weeks followed by 100mg/kg/bw ABT-263 treatment on WD for 6 weeks. (G) Probability of survival (Kaplan-Meier curve). (H) Representative confocal images of co-staining for eYFP (for detecting EC), α-SMA⁺, and DAPI in advanced BCA lesions from experiment F. (I) Quantification of the percentage of EC-derived Cdh5-eYFP⁺ DAPI⁺ cells in the fibrous cap, and (J) quantification of the percentage of EC-derived α-SMA⁺ (Cdh5-eYFP+ α-SMA⁺/ α-SMA⁺) cells in the fibrous cap. The two-way ANOVA method was used for statistical analyses in C-E and H-J. Biologically independent animals are indicated as individual dots. Error bars are shown with the SEM. A Mantel-Cox test was used for G. The p-values are indicated on the figures.