Protective effect of human apo AI overexpression on atherogenesis in transgenic rabbit

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• 作者：Tailleux ; A. ; Hennuyer ; N. ; Caillaud ; J.M. ; Emmanuel ; F. ; Fruchart ; J.C. ; Duverger ; N. ; Fievet ; C.
• 刊名：Atherosclerosis
• 出版年：1997
• 期刊代码：28_00219150
• 类别：med
• 出版时间：October, 1997
• 卷：134
• 期：1-2
• 页码：35
• 文件大小：148 K

摘要

Prospective epidemiological studies in human have suggested that high levels of HDL and of its major protein component apo AI directly decrease the development of atherosclerosis. This hypothesis has to be confirmed in vivo in animal models of atherosclerosis that resembles the human disease. Rabbit model is appropriate to demonstrate the precise role of apo AI in limiting the progression of atherogenesis. Cholesterol-fed human apo AI New Zealand white transgenic rabbits are significantly protected from the development of aortic fatty-streak lesions and lipid accumulation (Duverger et al., Circulation 1996, 94: 713-717). However, to evaluate the effect of the apo A-I transgene on atherosclerosis development, the authors adjusted the dose of cholesterol in the diet to produce the same level of non HDL cholesterol in the plasma of the animals. Therefore, the enrichment was lower in the diet for transgenics. In the present study, human apo A-I transgenic rabbits (n = 12) and control rabbits (n = 8) were fed with a same cholesterol-rich diet (0.5%) for 14 weeks in order to evaluate the effect of apo AI on the development of atherosclerosis. Plasma level of human apo AI ranged from 107 to 212 mg/ml (mean ± sd: 157 ± 33 mg/dl). The levels of HDL-cholesterol in transgenic group were higher than in control group (20 ± 6 versus 13 ± 4 mg/dl at 14 weeks; p < 0.05). At the same time, non-HDL cholesterol levels in transgenic group were higher than in control group but the difference was not significant (2175 ± 587 mg/dl) versus 1803 ± 806 mg/dl). At the end of 14 weeks, the aortic surface area covered by lesions was significantly less in transgenic rabbits compared with the control group (33 ± 13%versus 44 ± 19%, p < 0.001) despite 98%of total cholesterol was carried by atherogenic lipoproteins (VLDL, LDL) in both animal groups. Thus, the protective effect of the human apo AI transgenic on atherosclerosis must be related to the higher levels of HDL cholesterol and apo AI in the plasma of the transgenic animals.