A novel mouse model of autologous venous graft intimal hyperplasia

J Surg Res. 2005 Jun 1;126(1):106-13. doi: 10.1016/j.jss.2005.01.025.

Abstract

Background: To investigate the molecular mechanism of autologous venous graft intimal hyperplasia, a mouse model is needed. Currently only vein to carotid artery mouse models are available and are hampered by a high thrombosis rate. We hypothesized that operating on the aorta would lead to intimal hyperplasia with decreased risk of thrombosis.

Materials and methods: In C57BL/6J mice, the left external jugular vein was grafted into the infrarenal abdominal aorta by end-to-end anastomosis with 11-0 Ethilon. Grafts harvested at 1, 2, 4, 8, and 16 weeks postoperatively were subjected to histological and immunohistochemical analysis.

Results: Thirty-one of 35 mice survived; 2 mice were sacrificed secondary to thrombosis. The percentage lumen narrowing (+/-SE) was 7.8 +/- 0.3, 16.4 +/- 0.9, 19.2 +/- 0.9, 22.3 +/- 0.8, and 23.9 +/- 1.6% at 1, 2, 4, 8 and 16 weeks, respectively. Nuclear density decreased with each successive time point. The percentage of alpha-smooth-muscle actin-positive cells within the neointima peaked at 16 weeks (53%), and the percentage of cells positive for proliferating cell nuclear antigen peaked at 2 weeks (39%).

Conclusions: We thus report on a novel mouse model of intimal hyperplasia in autologous venous grafts with a low thrombosis rate. Further studies using this model, coupled with genetic and bone marrow transplantation mouse models, should lead to significant enhancement in understanding of the mechanism of intimal hyperplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Disease Models, Animal
  • Hyperplasia
  • Jugular Veins / transplantation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / pathology
  • Proliferating Cell Nuclear Antigen / analysis
  • Transplantation, Autologous
  • Tunica Intima / pathology*

Substances

  • Proliferating Cell Nuclear Antigen