C57BL/6 NK cell gene complex is crucially involved in vascular remodeling

Abstract

ObjectiveNK cells are known to be involved in cardiovascular disease processes. One of these processes, vascular remodeling, may strongly differ between individuals and mouse strains such as the C57BL/6 and BALB/c. Moreover, C57BL/6 and BALB/c mice vary in immune responses and in the composition of their Natural Killer gene Complex (NKC). Here we study the role of NK cells, and in particular the C57BL/6 NKC in vascular remodeling and intimal hyperplasia formation. Methods and resultsC57BL/6, BALB/c and CMV1r mice, a BALB/c strain congenic for the C57BL/6 NKC, were used in an injury induced cuff model and a vein graft model. NK cell depleted C57BL/6 mice demonstrated a 43% reduction in intimal hyperplasia after femoral artery cuff placement compared to control C57BL/6 mice (p<0.05). Cuff placement and vein grafting resulted in profound intimal hyperplasia in C57BL/6 mice, but also in CMV1r mice, whereas this was significantly less in BALB/c mice. Significant more leukocyte infiltrations and IFN-γ staining were seen in both C57BL/6 and CMV1r vein grafts compared to BALB/c vein grafts. ConclusionsThese data demonstrate an important role for NK cells in intimal hyperplasia and vascular remodeling. Furthermore, the C57BL/6 NKC in CMV1r mice stimulates vascular remodeling most likely through the activation of (IFN-γ-secreting) NK-cells that modulate the outcome of vascular remodeling.