Figure 8. Treatment of Apoe^–/– mice with advanced lesions with a reduced dose (50mg/kg/bw) of ABT-263 decreased collagen content within BCA lesions and was also associated with increased mortality.

(A) Experimental design. EC lineage tracing Apoe^–/– mice were fed a WD for 18 weeks followed by 50 mg/kg/bw ABT-263 treatment on WD for 9 weeks. (B) Probability of survival (Kaplan-Meier curve). (C) Representative 10× images of MOVAT staining of the BCA. Scale bar: 100 μm. (D) Lesion area from C. (E) Lumen area from C. (F) External elastic lamina (EEL) area from C, for outward remodeling. (G) Necrotic core area normalized to lesion size. (H) Representative 10× images of Picrosirius red staining on BCA. Scale bar: 100 μm. (I) Quantification of mature (red) collagen content normalized to lesion area from H. (J) Representative confocal images of costaining for eYFP (for detecting EC), α-SMA⁺, and DAPI in advanced BCA lesions. Scale bars: 100 μm. (K) α-SMA⁺ cap area normalized to lesion area (α-SMA⁺ cap area/lesion area). (L) Quantification of the percentage α-SMA⁺ (α-SMA⁺/DAPI) cells in the fibrous cap. (M) Quantification of the percentage EC-derived (Cdh5-eYFP⁺/DAPI⁺) cells in the lesion. (N) Quantification of the percentage EC-derived α-SMA⁺ (Cdh5-eYFP⁺ α-SMA⁺/α-SMA⁺) cells in lesions. The 2-way ANOVA method was used for statistical analysis in D, G, and K–L, and biologically independent animals are indicated as individual dots. Data are shown as mean ± SEM. A Mantel-Cox test was used for statistical analysis in B. The P values are indicated on the respective graphs.