The lack of effect of beta-carotene on restenosis in cholesterol-fed rabbits

The success of percutaneous transluminal coronary angioplasty is limited by restenosis in 30-50% of cases. Cellular production of reactive oxygen species at the site of injury has been implicated as a contributing factor in the process of restenosis. beta-Carotene is a lipid-soluble antioxidant whose effects on this process have not been previously investigated. We attempted to elucidate whether beta-carotene treatment was capable of reducing restenosis. Femoral artery stenoses were produced by nitrogen-desiccation in rabbits fed a high-cholesterol diet. The animals were randomized to receive either a parenteral bolus of beta-carotene immediately prior to angioplasty, followed by 5 days of subcutaneous treatment (Acute Treatment); 5 days of subcutaneous pretreatment with beta-carotene followed by a parenteral bolus immediately prior to angioplasty and then another 5 days of subcutaneous treatment (Pretreatment); or vehicle only (Control). Angiography was performed immediately before and after angioplasty, and 28 days after angioplasty. The animals were then sacrificed, and the femoral arteries were harvested for histopathology. By quantitative angiography, the late loss of luminal diameter between angioplasty and final angiography was not significantly different between the acute treatment group, the pretreatment group and the control group. By histopathology, the area of intimal hyperplasia and the percent cross-sectional area stenosis were also not significantly different. The late loss in luminal diameter after angioplasty correlated significantly with the acute gain in luminal diameter produced by angioplasty. The amount of intimal hyperplasia correlated significantly with the arterial injury score assessed by histopathology. In summary, in this animal model of restenosis, parenteral beta-carotene failed to significantly reduce the amount of either intimal hyperplasia or late loss in luminal diameter after angioplasty.