A novel model of accelerated intimal hyperplasia in the pig iliac artery

Int J Exp Pathol. 2011 Dec;92(6):422-7. doi: 10.1111/j.1365-2613.2011.00790.x. Epub 2011 Nov 3.

Abstract

There is no good animal model of large artery injury-induced intimal hyperplasia (IH). Those available are reproducible, providing only a few layers of proliferating cells or have the disadvantage of the presence of a metallic stent that complicates histology evaluation. This study was designed to develop a new, simple model of accelerated IH based on balloon injury in conjunction with disruption of the Internal Elastic Lamina (IEL) in pig external iliac arteries. Iliac artery injury (n = 24) was performed in 12 Yorkshire pigs divided in two groups: Group I (n = 10), overdistention injury induced by an oversized non-compliant balloon; Group II (n = 14), arterial wall disruption by pulling back an isometric cutting balloon (CB) followed by stretching with a compliant Fogarty Balloon (FB). At two weeks, arteries were processed for morphometric analysis and immunohistochemistry (IHC) for smooth muscle cells (SMC) and proliferating cell nuclear antigen (PCNA). When comparing the two groups, at 2 weeks, arteries of group II had a higher incidence of IH (100%vs. 50%, P = 0.0059), increased intimal areas (2.54 ± 0.33 mm(2) vs. 0.93 ± 0.36 mm(2) , P = 0.004), increased intimal area/Media area ratios (0.95 ± 0.1 vs. 0.28 ± 0.05; P < 0.0001) and decreased lumen areas (6.24 ± 0.44 vs. 9.48 ± 1.56, P = 0.026). No thrombosis was noticed in Group II. Neointima was composed by proliferating SMC located with the highest concentration in the area of IEL disruption (IHC). Arterial injury by pulling back CB and FB induces significant IH in pig iliac arteries by two weeks without thrombosis. This model is superior to the classical overdistention non-compliant model and should be useful and cost-effective for preclinical testing of procedures designed to inhibit IH in large peripheral arteries.

MeSH terms

  • Animals
  • Catheterization / adverse effects*
  • Cell Proliferation
  • Disease Models, Animal*
  • Hyperplasia / etiology
  • Hyperplasia / pathology
  • Iliac Artery / metabolism
  • Iliac Artery / pathology*
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Neointima / metabolism
  • Neointima / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Swine
  • Time Factors
  • Tunica Intima / metabolism
  • Tunica Intima / pathology*
  • Tunica Media / metabolism
  • Tunica Media / pathology

Substances

  • Proliferating Cell Nuclear Antigen