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

J Mol Cell Cardiol. 2013 Nov:64:51-8. doi: 10.1016/j.yjmcc.2013.08.009. Epub 2013 Sep 5.

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.

Methods and 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.

Keywords: Cardiovascular disease; IFN-γ; Intimal hyperplasia; NK cell gene complex; NK cells; Vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / immunology
  • Arteries / metabolism
  • Arteries / pathology
  • Blood Vessels / immunology
  • Blood Vessels / metabolism*
  • Blood Vessels / pathology*
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Hyperplasia
  • Inflammation / genetics
  • Inflammation / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Tunica Intima / immunology
  • Tunica Intima / metabolism*
  • Tunica Intima / pathology*
  • Veins / immunology
  • Veins / metabolism
  • Veins / pathology