Expression of Apolipoprotein A-I in Rabbit Carotid Endothelium Protects Against Atherosclerosis
Expression of Apolipoprotein A-I in Rabbit Carotid Endothelium Protects Against Atherosclerosis
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DOI：
10.1038/mt.2011.133
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发表时间：
2011-10-01
影响因子：
12.4
通讯作者：
Dichek, David A.
中科院分区：
文献类型：
--
作者：
Flynn, Rowan;Qian, Kun;Dichek, David A.
动脉粥样硬化保护基因在血管壁中的表达可能是预防或逆转动脉粥样硬化的有效手段。由于缺乏合适的基因转移载体，这种方法的发展受到阻碍。我们使用辅助依赖性腺病毒（HDAd）载体来检测载脂蛋白A-I（apoA-I）在动脉壁中的表达是否可以延缓高血压兔动脉粥样硬化的发展。将表达兔apoA-I的HDAd或“空”HDAd注入颈动脉，并在2周和4周后收获。ApoA-I mRNA和蛋白仅在HDAdApoAI动脉中检测到。2周时，两组的病变大小、脂质和巨噬细胞含量以及粘附分子表达相似。在第2周和第4周之间，大多数动脉粥样硬化指标在HDAd-ApoAI动脉中增加，但在HDAdApoAI动脉中稳定或减少（P = 48周，从4周到48周载体DNA含量和apoA-I表达稳定。载脂蛋白A-I在动脉内皮中的表达显著延缓动脉粥样硬化。HDAd在动脉壁中提供治疗性转基因的延长的、稳定的表达。收稿日期：2011年3月2日;接受日期：2011年6月6日;在线发表
Expression of atheroprotective genes in the blood vessel wall is potentially an effective means of preventing or reversing atherosclerosis. Development of this approach has been hampered by lack of a suitable gene-transfer vector. We used a helper-dependent adenoviral (HDAd) vector to test whether expression of apolipoprotein A-I (apoA-I) in the artery wall could retard the development of atherosclerosis in hyperlipidemic rabbits. Carotid arteries were infused with an HDAd expressing rabbit apoA-I or a "null" HDAd and harvested 2 and 4 weeks later. ApoA-I mRNA and protein were detected only in HDAdApoAI arteries. Lesion size, lipid and macrophage content, and adhesion molecule expression were similar in both groups at 2 weeks. Between 2 and 4 weeks, most of these measures of atherosclerosis increased in HDAd-Null arteries, but were stable or decreased in HDAdApoAI arteries (P = 48 weeks, with stable vector DNA content and apoA-I expression from 4 to 48 weeks. Expression of apoA-I in arterial endothelium significantly retards atherosclerosis. HDAd provides prolonged, stable expression of a therapeutic transgene in the artery wall. Received 2 March 2011; accepted 6 June 2011; published online