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: 28±5% versus 81±13% at day 4; P=0.003 and 57±12% versus 107±8% at day 7; P=0.003). Vessel measurements of α-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, α-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.

Cell movement, Chemokine CXCL10, Inflammation, interferon-γ-inducible protein of 10 kDa, Myocytes, smooth muscle
dx.doi.org/10.1161/ATVBAHA.113.303050, hdl.handle.net/1765/67395
Arteriosclerosis, Thrombosis, and Vascular Biology
Department of Cardiology

van den Borne, P, Haverslag, R.T, Brandt, M.M, Cheng, C, Duckers, H.J, Quax, P.H.A, … de Kleijn, D.P.V. (2014). Absence of chemokine (C-X-C Motif) ligand 10 diminishes perfusion recovery after local arterial occlusion in mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(3), 594–602. doi:10.1161/ATVBAHA.113.303050