Abstract 150: Natural Killer Cells Are Crucially Involved in Vascular Remodeling and Intimal Hyperplasia
Introduction Immune cells such as monocytes and T cells but also NK cells are proven contributors to atherosclerosis. Interestingly, C57BL/6 mice display profound induced vascular remodeling in arteriogenesis whereas BALB/c mice show less remodeling. Moreover, these two strains differ in their NK cell receptor gene complex (NKC), which codes for activating and inhibitory NK cell receptors. We hypothesize that NK cells are crucially involved in vascular remodeling and intimal hyperplasia formation.
Methods and Results Vascular remodeling was studied in two models; injury induced restenosis by femoral artery cuff placement and vein graft remodeling by placement of a caval vein interpositioning in the mouse carotid artery.
NK cell depletion with NK1.1 antibodies in C57BL/6 mice showed significant less (2266um2) cuff-induced intimal hyperplasia than control mice (5252um2) did. Similar results were found in NK-cell deficient mice, which showed an intimal hyperplasia of (2261um2) after cuff-placement compared to control mice (3279um2). After cuff-placement in CMV1r mice which are congenic for the C57BL/6 NKC, an intimal hyperplasia of 4745um2 was found, comparative to C57BL/6 (4459um2), and significantly more than BALB/c mice (1247um2).
CMV1r mice showed stronger intimal hyperplasia in vein grafts (0.22mm2) compared to both C57BL/6 (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 NK cell 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 NK cells but more specific, 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 strains strongly suggest that the C57BL/6 NK receptor repertoire might be involved in triggering an immune response that is associated with vascular remodeling.
- © 2012 by American Heart Association, Inc.