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  • Title: Persistence of balloon-induced arterial injury with hyperlipidemia despite gemfibrozil.
    Author: Lundgren C, Sobel BE, Fujii S.
    Journal: Jpn Heart J; 1996 Jan; 37(1):119-26. PubMed ID: 8632619.
    Abstract:
    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.
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