CELL-PROLIFERATION AFTER BALLOON INJURY OF ILIAC ARTERIES IN THE CHOLESTEROL-FED NEW-ZEALAND WHITE-RABBIT

Acute mechanical injury of an artery results in neointimal hyperplasia that is due at least in part to cell proliferation within the vessel wall. The purpose of this study was to quantify cell proliferation act ivity in the iliac artery of New Zealand White rabbits after balloon i njury and cholesterol feeding. Retrograde pullback balloon injury of i liac arteries was performed, and the animals were then fed a 2% choles terol diet. At intervals from day 1 through day 35 postinjury, iliac a rteries were obtained for histological analysis. Intimal and medial ar eas were measured morphometrically. Total number of cells within the i ntima and media was counted. Smooth muscle cell-predominant or macroph age predominant regions of the intima and media were identified using HHF-35 and RAM-11 immunocytochemical markers, respectively. Number of cells in the proliferative phase of the cell cycle was measured by usi ng the proliferating cell nuclear antigen and bromodeoxyuridine techni ques. Thirty-one arteries from 16 rabbits were available for analysis. Total number of cells and number of cells per square millimeter withi n the media did not change significantly from day 1 through day 35 pos tinjury. Total number of cells within the intima increased significant ly, but the number of cells per square millimeter of intima decreased significantly during the same time period. Proliferative activity was identified in the media between days 3 and 35 with peak activity at da y 3 postinjury. Proliferative activity in the intima was present in al l specimens from day 8 through day 35. Proliferative activity was pres ent in both HHF-35- and RAM-11-predominant regions of the intima. Prol iferative activity in the intima exceeded that in the media (P<.0001 b y MANOVA), particularly during day 8 through day 13 and on day 21 post injury. The time course of cell proliferation activity documented in t his model is similar to the time course of cell proliferation activity in two other models of injury of normal arteries. However, the spatia l orientation of proliferative activity in the intima and the involvem ent of RAM-11-predominant regions-presumably macrophages-in the prolif erative response represent factors that appear unique to this choleste rol-fed model of acute arterial injury.