title: C57BL/6 NK cell gene complex is crucially involved in vascular remodeling.
abstract: OBJECTIVE
  NK 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.
  
  
  RESULTS
  C57BL/6, BALB/c and CMV1(r) 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 CMV1(r) 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 CMV1(r) vein grafts compared to BALB/c vein grafts.
  
  
  CONCLUSIONS
  These data demonstrate an important role for NK cells in intimal hyperplasia and vascular remodeling. Furthermore, the C57BL/6 NKC in CMV1(r) mice stimulates vascular remodeling most likely through the activation of (IFN-γ-secreting) NK-cells that modulate the outcome of vascular remodeling.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: de Vries
authors.forename: L
authors.initials: L
authors.lastname: Seghers
authors.forename: J
authors.initials: J
authors.lastname: van Bergen
authors.forename: H A B
authors.initials: HA
authors.lastname: Peters
authors.forename: R C M
authors.initials: RC
authors.lastname: de Jong
authors.forename: J F
authors.initials: JF
authors.lastname: Hamming
authors.forename: R E M
authors.initials: RE
authors.lastname: Toes
authors.forename: V W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: P H A
authors.initials: PH
authors.lastname: Quax
mesh_terms: D000818:Animals; D001158:Arteries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006965:Hyperplasia; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D014680:Veins / Q000276:immunology / Q000378:metabolism / Q000473:pathology
keywords: Cardiovascular disease; IFN-γ; Intimal hyperplasia; NK cell gene complex; NK cells; Vascular remodeling