Absence of Chemokine (C-X-C Motif) Ligand 10 Diminishes Perfusion Recovery After Local Arterial Occlusion in Mice

P van den Borne, RT Haverslag, Maarten Brandt, Caroline Cheng, HJ Duckers, PHA Quax, IE Hoefer, G Pasterkamp, DPV de Kleijn

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Objective In arteriogenesis, pre-existing anastomoses undergo enlargement to restore blood flow in ischemic tissues. Chemokine (C-X-C motif) ligand 10 (CXCL10) is secreted after Toll-like receptor activation. Toll-like receptors are involved in arteriogenesis; however, the role of CXCL10 is still unclear. In this study, we investigated the role for CXCL10 in a murine hindlimb ischemia model. Approach and Results Unilateral femoral artery ligation was performed in wild-type (WT) and CXCL10(-/-) knockout (KO) mice and perfusion recovery was measured using laser-Doppler perfusion analysis. Perfusion recovery was significantly lower in KO mice compared with WT at days 4 and 7 after surgery (KO versus WT: 285% versus 81 +/- 13% at day 4; P=0.003 and 57 +/- 12% versus 107 +/- 8% at day 7; P=0.003). Vessel measurements of -smooth muscle actin-positive vessels revealed increasing numbers in time after surgery, which was significantly higher in WT when compared with that in KO. Furthermore, -smooth muscle actin-positive vessels were significantly larger in WT when compared with those in KO at day 7 (wall thickness, P<0.001; lumen area, P=0.003). Local inflammation was assessed in hindlimb muscles, but this did not differ between WT and KO. Chimerization experiments analyzing perfusion recovery and histology revealed an equal contribution for bone marrow-derived and circulating CXCL10. Migration assays showed a stimulating role for both intrinsic and extrinsic CXCL10 in vascular smooth muscle cell migration. Conclusions CXCL10 plays a causal role in arteriogenesis. Bone marrow-derived CXCL10 and tissue-derived CXCL10 play a critical role in accelerating perfusion recovery after arterial occlusion in mice probably by promoting vascular smooth muscle cell recruitment and maturation of pre-existing anastomoses.
Original languageUndefined/Unknown
Pages (from-to)594-602
Number of pages9
JournalArteriosclerosis Thrombosis & Vascular Biology
Issue number3
Publication statusPublished - 2014

Research programs

  • EMC COEUR-09

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