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. 2022 Mar 23;118(17):3346–3359. doi: 10.1093/cvr/cvac032

Figure 2.

Figure 2

Ferumoxide and ferumoxtran increased apoptosis in atherosclerotic lesions in hyperlipidaemic ApoE−/− and LDLR−/− mice. (A) ApoE−/− mice with advanced atherosclerosis were injected once with NaCl 0.9% (n = 3), ferumoxide (0.3 mg Fe/kg; n = 3), or ferumoxtran (1 mg Fe/kg; n = 3). TUNEL-positive cells in the atherosclerotic plaques of the aortic root were quantified and normalized to total cell count. *P < 0.05 for Kruskal–Wallis across three groups, no significant changes in Dunn’s post hoc testing between individual groups. (B) Representative image of TUNEL staining of plaques in control, (C) ferumoxide, or (D) ferumoxtran-treated mice. Scale bar in (B) to (D) corresponds to 100 μm. (E) Plaque area of ApoE−/− was determined by computer-assisted morphometric analysis of Oil red O-stained section. (F) The percentage of TUNEL-positive cells was quantified in liver and (G) spleen of ApoE−/− mice controls and mice receiving a single ferumoxide or ferumoxtran dose. *P < 0.05 for Kruskal–Wallis across three groups, #P < 0.05 in Dunn’s post hoc testing vs. control. (H) LDLR−/− mice with initial plaques were fed a high cholesterol diet and received weekly intravenous injections with NaCl 0.9% (control group, n = 8) or ferumoxtran (n = 8). The percentage of TUNEL-positive cells was quantified in the atherosclerotic plaques of the aortic root. Unpaired Student’s t-test, *P < 0.05 and ***P < 0.001 compared with control conditions. (I) Representative image of TUNEL staining of plaques in control and (J) ferumoxtran-treated LDLR−/− mice. (K) Plaque area (Oil red O) and (l) the percentage of macrophages (MoMa-2-positive) cells were quantified in plaques of control LDLR−/− and mice repeatedly treated with ferumoxtran. Statistics: unpaired Student’s t-test, *P < 0.05 and ***P < 0.001 compared with control conditions. Data are mean ± SEM. CON, control.