Abstract 14649: C57BL/6 Nk Cell Gene Complex Crucially Involved in Vascular Remodeling and Intimal Hyperplasia
Introduction Immune cells as monocytes, CD4+ and CD8+ T-cells but also NK-cells are proven contributors to atherosclerosis and vascular remodelling. Interestingly, C57BL/6 mice display profound induced vascular remodeling, eg in arteriogenesis and restenosis, whereas BALB/c mice display less remodeling. Moreover, these two strains are different in their NK-cell receptor gene complex (NKC), which codes for activating and inhibitory NK-cell receptors. We hypothesize that C57BL/6 NKC is crucially involved in vascular remodeling and intimal hyperplasia.
Methods and Results C57BL/6, BALB/c mice and the BALB.B6-CMV1r (CMV1r) strain, which is congenic for the C57BL/6 NKC, were used in two models of vascular remodeling; injury induced restenosis by femoral artery cuff placement and vein grafting by placement of a caval vein interposition in the mouse carotid artery. After cuff-placement the congenic CMV1r mice showed progressive formation of intimal hyperplasia (4745 um2), comparative to C57BL/6 (4459 um2), and significantly more than BALB/c mice (1247 um2), that displayed very little intimal hyperplasia. Vein graft remodeling in CMV1r 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, CMV1r displayed equal amounts of CD45 positive cells to that of C57BL/6 mice, whereas BALB/c mice show hardly any leukocyte influx into the vessel wall. Flow cytometric analysis of NKcell responsiveness to specific NK receptor mediated activation by NKp46 in C57BL/6, BALB/c and CMV1r splenic NK-cells resulted in a significantly improved responsiveness of CMV1 r NK-cells when compared to BALB/c NK-cells to the level of C57BL/6 NK-cells.
Conclusion: These data demonstrate that the C57BL/6 NK-cell gene locus is involved in the induction of vascular remodeling. Furthermore, the observed differences in inflammatory infiltrate and NK-cell responsiveness 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 vascular remodeling.
- © 2011 by American Heart Association, Inc.