Background – Venous grafts (VG) are the most used conduit in re-building arterial circulation in clinic. However, VGs degenerate easily after being implanted in the arterial circulation system. Intimal hyperplasia (IH) is the major cause of VG failure. The role of selectin-dependent leukocyte recruitment in development of IH in VG is still unclear. Methods – VGs were studied at different time points postoperatively (Time 0, 7, 28, 63 days). VG implantation was performed by cuff fashion of the thoracic vena cava from donor mice to left carotid artery in recipients. The development of IH after VG implantation was studies by histology. Intravital microscopy was used to study interactions between leukocytes and endothelium in the native vessels and in transferred graft. VG in P- and E-selectin deficiency mice (PE-/- mice) and P-selectin deficiency mice (P-/- mice) display the effect of selectin in intimal hyperplasia. For the role of selectin-dependent leukocyte recruitment in VG, wild type mice (WT mice) transferred with VG were injected by mixture of rat anti-mouse P-selectin (100 μg, clone RB40.34) and rat anti-mouse E-selectin functional (100 μg, clone 9A9) blocking antibody through experimental time. Early single bolus of rat anti-mouse P-selectin antibody (200 μg, clone RB40.34), or early single bolus of rat anti-mouse PSGL-1 antibody (200 μg, clone 4RA10) in WT mice with VG was used to clarify the effect of P-selectin in early period after venous grafting. Immunohistochemistry showed the infiltration of leukocyte in IH of VG. Results- Intravital microscope showed less rolling and adhesive numbers of leukocytes along venous graft endothelium in PE-/- mice during entire experimental period whereas PE-/- mice had much higher circulating leukocytes. IH developed well in VG by 28 days in WT mice. In PE-/- mice and P-/- mice, VG developed less IH compared to WT mice up to 63 days post-transfer. Moreover, P-/E-section mixture antibody injection induced reduction of IH and the number of leukocyte infiltration in WT mice VG at 28 days after transferred. Early single bolus of P-selectin antibody injection led to similar IH reduction and decreased number of leukocyte infiltration in VG IH by 28 days. At the same time, early single bolus of PSGL-1 antibody showed less IH reduction and number decreasing in leukocyte infiltration at 28 days. Conclusions – P-/E-Selectin-dependent leukocyte recruitment is an important factor in development of intimal hyperplasia of venous graft. Functional blocking of P-and E-selectin can decrease the recruitment of leukocyte and subsequent leukocyte infiltration in IH of VG. Early single P-selectin functional blocking inhibited leukocyte recruitment and led to late IH reduction. P-selectin antagonist or combined P-/E-selectin antagonist could be a potential choice to prevent IH after VG transferred.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD362
Poster Communications: Blocking selectin reduced late intimal hyperplasia in vein graft in mice
C. Tseng1, Y. Chang1, M. Kronqvist1, M. Lengquist1, U. Hedin1, E. E. Eriksson1
1. Karolinska institutet, Stockholm, Sweden.
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Where applicable, experiments conform with Society ethical requirements.