Angiopoietin trapping delays hemangiogenic recovery. (A) Disruption of the angiopoietin signal disturbs BM vascular remodeling after chemotherapy. Wild-type mice received a single tail-vein injection of AdTie2-Fc one day after a single tail-vein dose of 250 mg/kg 5-FU (n = 12). At the indicated time points, 3 mice were killed, and BM was obtained for histologic analysis. Hematoxylin and eosin–stained paraffin sections highlight vascular changes during hemangiogenic reconstitution. These histologic studies demonstrate that the inhibition of angiopoietin signaling after myelosuppression results in impaired assembly of neovessels with a delayed reconstruction of the BM microarchitecture. On day 10, there is an accumulation of polyploid megakaryocytes entrapped within the BM, dissociated from the sinusoidal endothelial cells, resulting in thrombocytopenia (blue arrows). In addition, on day 14, the newly formed sinusoids were still dilated and irregular, displaying features of unstabilized neovessels (yellow arrows). (B) Introduction of Tie2-Fc diminishes peripheral blood-cell concentration both at steady state and after myelosuppression. (Left) AdTie2-Fc results in a decrease of platelet levels by 60% to that observed at steady state (n = 6, P < .01 on day 7). Compared with control mice, AdTie2-Fc inhibits rebound thrombocytosis and delays thrombopoietic recovery after myelosuppression (n = 6, P < .02 at day 15). All data are expressed as the mean ± SEM. (Right) Similar changes are seen in the white blood cells (n = 6).