Abstract 5775: C57BL/6 NK Cell Gene Complex Crucially Involved in General Vascular Remodelling

Abstract

Background The immune system plays an important role in vascular remodelling. Inflammatory cells as monocytes, CD4+ and CD8+ T cells were already proven to be modulators of vascular remodelling. Recently, NK cells were indicated to contribute to vascular remodelling in processes of revascularisation and atherosclerotic lesion development. Interestingly, C57BL/6 mice display profound induced vascular remodelling, eg in arteriogenesis, restenosis and vein grafting, whereas BALB/c mice display much less remodelling. Moreover, these two mouse strains are different in their NK cell receptor gene complex (NKC), which codes for activating and inhibitory NK cell receptors. Aim To demonstrate that C57BL/6 NKC is crucially involved in modulating vascular remodelling in general. Material & Methods C57BL/6, BALB/c and BALB.B6- CMV1 r (CMV1 r ) mice, of which the latter is congenic for the C57BL/6 NKC, were used in two different models of vascular remodelling, induction of restenosis by femoral artery cuff placement and vein grafting by placement of a venous interposition in the mouse carotid artery. Vascular remodelling was monitored by morphometry and immunohistology. Results After cuff-placement the congenic CMV1r mice showed progressive formation of neointima (4745 um2), comparative to C57BL/6 (4459 um2), and significantly more than BALB/c mice (1247 um2), that displayed very little formation of neointima. Vein graft remodelling in CMV1 r mice showed stronger intimal hyperplasia in vein grafts (0.22mm2) compared to both C57BL/6 mice (0.15mm2) and BALB/c mice (0.11mm2). Importantly, CMV1 r displayed an inflammatory infiltrate similar to that of C57BL/6 mice, whereas BALB/c mice show hardly any inflammatory cell influx into the vessel wall. Conclusion These data demonstrate that the C57BL/6 NK cell gene locus is involved in the induction of profound vascular remodelling in general. Furthermore, the observed differences in inflammatory infiltrate between the three mouse strains strongly suggest that the C57BL/6 NK receptor repertoire might be involved in triggering an immune response that is associated with profound vascular remodelling.