Flow-responsive remodeling after angioplasty is enhanced by high cholesterol diet. Prevention with pyrrolidine dithiocarbamate

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• 作者：Ward ; Michael R. ; Tsao ; Philip S. ; Herity ; Niall A. ; Cooke ; John P. ; Yeung ; Alan C.
• 关键词：Restenosis ; Atherosclerosis ; Remodeling ; Cholesterol ; Free radicals
• 刊名：Atherosclerosis
• 出版年：2003
• 期刊代码：28_00219150
• 类别：med
• 出版时间：June, 2003
• 卷：168
• 期：2
• 页码：333-341
• 文件大小：279 K

摘要

We examined the effects of high cholesterol diet and pyrrolidine dithiocarbamate (PDTC) on flow-dependent remodeling after angioplasty. After right common carotid balloon-injury, the right external carotid (low flow) or left common carotid artery were ligated (high flow) in rabbits fed normal diet, 1%cholesterol diet without or with the antioxidant PDTC for 7 days pre- and 7–28 days post-injury. Angiographic lumen diameter was significantly greater at 28 days in high flow than low flow normal diet animals, attributable on perfusion-fixed vessel morphometry to altered remodeling (area within the external elastic lamina: high flow 1.85±0.24 vs. low flow 1.31±0.04 mm², P<0.05) rather than differences in neointima formation or vessel tone. In animals on 1%cholesterol diet high flow remodeling was significantly enhanced (area within the external elastic lamina 3.13±0.17 mm², P<0.05 vs. high flow normal diet) but low flow inward remodeling was similar (area within the external elastic lamina 1.29±0.07 mm²). Mean Doppler flow velocities (initial/post-ligation/28 day follow-up, cm/s) had almost normalized in normal diet animals (high flow 30/49/35, low flow 32/9/26) but showed overcompensation in 1%cholesterol diet animals (high flow 32/49/22, low flow 30/11/25). PDTC therapy markedly attenuated remodeling (area within the external elastic lamina: high flow 2.20±0.18, and low flow 2.00±0.11 both P<0.05 vs. 1%cholesterol diet alone) and flow velocities only partially normalized (high flow 26/42/34, low flow 27/7/16). We conclude that hypercholesterolemia enhances and PDTC attenuates flow-dependent remodeling after angioplasty.