Restenosis after balloon dilitation of atherosclerotic arteries reflects migration and proliferation of vascular smooth muscle cells and infiltration of monocyte/macrophages.
Hypercholesterolemia may contribute to this phenomenon. Accordingly, we used the
lipid-lowering agent
gemfibrozil to determine whether potentially detrimental effects of
hypercholesterolemia on
vascular remodeling after mechanical injury could be attenuated. New Zealand white rabbits fed either a chow diet (control), a 0.25%
cholesterol-enriched diet, or a 0.25%
cholesterol-enriched diet supplemented with
gemfibrozil (0.05%, 0.1%, or 0.02%) for one week were subjected to balloon-induced carotid injury and maintained on the same diet for an additional 4 weeks. Histology of the vascular wall was then characterized. Plasma
triglycerides before and 4 weeks after injury did not change in any of the treatment groups (p = 0.24). Plasma
cholesterol increased in all animals receiving the high
cholesterol diet, and the increases remained unaffected by supplementation with
gemfibrozil. In control rabbits, intimal thickening area [intima (mm2)/(intima + media (mm2))] 4 weeks after injury was 27.0 +/- 7.7% (n = 16). Values were the same in hypercholesterolemic rabbits (29.7 +/- 11.8%, n = 12; p = ns). However, in 16% the lumen was completely occluded by
thrombus and intimal thickening could not be quantified. In hypercholesterolemic rabbits given
gemfibrozil, intimal thickening was increased by 33% compared with controls (35.9 +/- 11.6%, n = 39, pound 0.05) and by 21% compared with hypercholesterolemic animals not given
gemfibrozil (p = ns). None had thrombotic
luminal occlusion. Macrophages detected immunohistochemically were only modest in number in vessels from control animals. In vessels from hypercholesterolemic animals and from animals whose diets were supplemented with
gemfibrozil, macrophages were increased in number in both intima and media. Thus,
gemfibrozil did not appear to attenuate processes implicated in restenosis. Its attenuation of thrombotic occlusion may be related to effects we have noted it exerts on fibrinolytic systems independent of lipid metabolism.