Abstract 18483: Absence of Chemokine (c-x-c Motif) Ligand 10 Diminishes Perfusion Recovery After Local Arterial Occlusion in Mice
Background In arteriogenesis, pre-existing anastomoses undergo enlargement into functional collateral arteries that are able to restore blood flow in ischemic tissues. Chemokine (C-X-C motif) ligand 10 (CXCL10) is secreted after Toll-like Receptor activation and involved in chemo-attraction of monocytes and T cells. Previously, we have shown that TLR2 and 4 are involved in arteriogenesis. In this study, we investigated the role of CXCL10 in the process of arteriogenesis.
Methods Unilateral femoral artery ligation was performed in wildtype (WT) and CXCL10-/- (KO) mice and perfusion recovery was measured over 7 days using Laser-Doppler analysis. Histology was performed in hind limb muscles for vessel number and influx of inflammatory cells. Chimerisation experiments were performed to assess the role of bone marrow-derived CXCL10. See table below for all animal numbers per experimental group. Data are shown as mean±SEM.
Results At 4 and 7 days after operation, perfusion recovery was significantly lower in KO mice compared to WT (50%±13 vs 35%±5 at day 4; p=0.003, 92%±2 vs 76%±13 at day 7; p=0.005) as well as numbers of vessels in the hind limb muscle (α-SMA, 102±7 vs 67±5 at day 4, p<0.001 and 88±9 vs 60±6 at day 7 p=0.02; CD-31, 102±7 vs 67±5 at day 4, p<0.001 and 74±14 vs 109±18 at day 7, p=0.02). Local macrophage and T cell infiltration did not significantly differ between WT and KO. Compared to WT, chimeric mice (KO bone marrow in WT) showed significantly lower perfusion recovery (WT vs chimers: 50%±13 vs 44%±4 at day 4 p=0.046, and 92%±2 vs 61%±5 at day 7, p<0.001). Compared to KO, chimeric mice (WT bone marrow in KO) showed significantly higher perfusion recovery, only at day 4 (KO vs chimers: 35%±5 vs 63%±4 at day 4, p<0.001, and 76%±13 vs 74%±6 at day 7, p=0.24).
Conclusions CXCL10 plays a critical role in arteriogenesis. Bone marrow-derived, as well as tissue derived CXCL10, plays a critical role in accelerating perfusion recovery after arterial occlusion in mice.
- © 2012 by American Heart Association, Inc.