Influence of Hypercholesterolemia on the Morphology of In-Stent Stenosis in an Experimental Animal Model

Post-mortem studies show that in-stent stenosis is characterized by a prolonged proliferation and inflammatory reactions around the stent struts. The aim of this study was to evaluate the influence of hypercholesterolemia on the specific characteristics of in-stent stenosis in an experimental animal model. Palmaz-Schatz stents were placed in the iliac arteries of 20 white New Zealand rabbits. One half of the animals were fed an 0.5% hypercholesterolemic diet, the other half were normocholesterolemic. After 28 days the animals were killed and the stented segments were excised. Immunohistochemistry with antibodies against bromodeoxyuridine, alpha-actin, RAM 11-macrophages and Von Willebrand factor was performed. Morphometric analysis was done on cuts with the stent left in place. Intimal and medial smooth-muscle-cell proliferation was significantly increased in hypercholesterolemic animals, mainly around the stent struts. Inflammatory infiltrates and clusters of macrophages were markedly increased as well, however, they were found predominantly at the edge of the stent, whereas proliferation was highest in the center of the stented segments. These effects contributed synergistically to a marked increase in neointimal stenosis (39% in hypercholesterolemic animals versus 26% in controls).