Figure 3.

Effects of ICI Treatment on Atherosclerosis

Male Ldlr^–/– mice on a high-cholesterol diet were treated twice a week with anti-CTLA-4 and anti-PD-1 antibodies (n = 15) or isotype control (n = 14) for 5 weeks. The aortic arch was analyzed. (A) Representative hematoxylin and eosin images of the aortic arch of control and ICI-treated mice. Scale bars represent 100 μm. (B) Analysis of plaque size in the aortic arch. (C) Virmani classification of aortic plaques from control and ICI-treated mice. In the latter group, fibrous cap atheromas (FCAs) and pathological intimal thickening (PIT) increased. (D) Quantification of necrotic core area as a percentage of plaque area. Histologic quantification of (E) CD45⁺ and (F) CD3⁺ cells in the aortic plaque. (G) Representative images of aortic arch CD8⁺ staining in control and ICI-treated mice. Scale bars represent 50 μm. (H) Quantification of CD8⁺ cells in the plaque. (I) Representative images of aortic arch MAC3 staining in control and ICI-treated mice. Scale bars represent 100 μm. (J) Analysis of MAC3-positive areas, represented as a percentage of total plaque area. (K) Ratio of CD3-positive to MAC3-positive areas in the aortic arch. (L) Histologic analysis of TUNEL⁺ (terminal deoxynucleotidyl transferase dUTP nick end labeling positive) cells in the aortic plaque. For all graphs, bars represent mean ± SEM. IX = intimal xanthoma; other abbreviations as in Figure 1.