Lundgren C, Sobel B E, Fujii S
Division of Cardiology, Wahington University School of Medicine, St. Louis, Missouri 63110, USA.
Jpn Heart J. 1996 Jan;37(1):119-26. doi: 10.1536/ihj.37.119.
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.
动脉粥样硬化动脉球囊扩张术后再狭窄反映了血管平滑肌细胞的迁移和增殖以及单核细胞/巨噬细胞的浸润。高胆固醇血症可能促成这一现象。因此，我们使用降脂药物吉非贝齐来确定高胆固醇血症对机械损伤后血管重塑的潜在有害影响是否可以减轻。给新西兰白兔喂食普通饲料（对照组）、含0.25%胆固醇的饲料或含0.25%胆固醇且补充吉非贝齐（0.05%、0.1%或0.02%）的饲料一周，然后对其进行球囊诱导的颈动脉损伤，并在相同饮食条件下再维持4周。随后对血管壁进行组织学分析。损伤前和损伤后4周，各治疗组的血浆甘油三酯均无变化（p = 0.24）。所有接受高胆固醇饮食的动物血浆胆固醇均升高，补充吉非贝齐对此升高无影响。在对照组兔子中，损伤后4周内膜增厚面积[内膜（mm²）/（内膜 + 中膜（mm²））]为27.0 +/- 7.7%（n = 16）。高胆固醇血症兔子的该值相同（29.7 +/- 11.8%，n = 12；p = 无显著差异）。然而，16%的管腔被血栓完全阻塞，内膜增厚无法量化。在给予吉非贝齐的高胆固醇血症兔子中，内膜增厚与对照组相比增加了33%（35.9 +/- 11.6%，n = 39，p < 0.05），与未给予吉非贝齐的高胆固醇血症动物相比增加了21%（p = 无显著差异）。无一例有血栓性管腔阻塞。免疫组化检测到的巨噬细胞在对照组动物血管中的数量仅为中等。在高胆固醇血症动物和饮食中补充吉非贝齐的动物的血管中，内膜和中膜中的巨噬细胞数量均增加。因此，吉非贝齐似乎并未减轻再狭窄相关的过程。其对血栓性阻塞的减轻作用可能与我们注意到的它对纤溶系统的作用有关，而与脂质代谢无关。
