Figure 1. Nilotinib exerts pro-atherogenic and anti-angiogenic effects in vivo.

(A) ApoE-/- mice were fed with a high-caloric lipid-diet and treated either with vehicle control (Control, 9 mice), Imatinib (50 mg/kg twice daily, 9 mice) or Nilotinib (37.5 mg/kg twice daily, 8 mice) for 8 weeks. Then, mice were sacrificed and their aortic roots were evaluated for plaque-formation. Results are expressed as percent of aortic areas affected by plaque-formation per mouse and show all mice in each group as well as median values (black bars). The difference in plaque-formation between the control group and Nilotinib group was statistically significant (p<0.05) by Mann-Whitney test. Overall, however, no statistically significant differences were found when comparing all three mouse groups by Kruskal Wallis test. (B) Hind-limb ischemia was induced in C57BL/6 wild-type mice by ligation of their left femoral artery. Thereafter, mice (13 mice per group) were treated with vehicle control, Imatinib (50 mg/kg twice daily) or Nilotinib (75 mg/kg/day) for 28 days. The ratio of blood flow in the ischemic versus non-ischemic limb was assessed by Laser Doppler Perfusion Imaging (LDPI). Results represent the mean±S.D. of all mice in each group. (C) Bone marrow sections were obtained from 7 CML patients before and after Nilotinib treatment for more than 1 year. Sections were stained using an antibody against CD34 to assess microvessel density. Results show microvessels per HPF and represent the mean±S.D. of all patients. Statistical tests: (B) Kruskal Wallis test; (C) Wilcoxon matched-pairs signed ranks test. *: p<0.05.