ADENOVIRUS-MEDIATED TRANSFER OF LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE ACUTELY ACCELERATES CHOLESTEROL CLEARANCE IN NORMAL MICE
ADENOVIRUS-MEDIATED TRANSFER OF LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE ACUTELY ACCELERATES CHOLESTEROL CLEARANCE IN NORMAL MICE
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DOI：
10.1073/pnas.90.7.2812
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发表时间：
1993-04-01
影响因子：
11.1
通讯作者：
GERARD, RD
中科院分区：
文献类型：
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作者：
HERZ, J;GERARD, RD
我们探索了使用腺病毒介导的基因转移来短暂诱导小鼠低密度脂蛋白（LDL）受体的产生。携带人类 LDL 受体 cDNA 的重组腺病毒恢复了受体缺陷培养细胞中的 LDL 受体功能。静脉注射重组病毒可显着降低正常小鼠的血浆胆固醇水平，并增加 I-125 标记的 LDL 从循环中的清除率。注射病毒后4天，血浆LDL的t1/2降低达10倍。根据 LDL 受体的免疫荧光或 β-半乳糖苷酶染色判断，估计肝脏中 90% 的实质细胞表达腺病毒转移的基因。这些结果表明，腺病毒介导的LDL受体基因转移提供了一种在短期内增强肝脏中LDL受体基因功能的有效方法。
We have explored the use of adenovirus-mediated gene transfer to transiently elicit production of low density lipoprotein (LDL) receptors in mice. A recombinant adenovirus carrying the human LDL receptor cDNA restored LDL receptor function in receptor-deficient cultured cells. Intravenous injection of recombinant virus acutely lowered plasma cholesterol levels and increased the rate of I-125-labeled LDL clearance from the circulation in normal mice. At 4 days after virus injection, the t1/2 of plasma LDL was reduced up to 10-fold. An estimated 90% of the parenchymal cells in liver expressed the adenovirus-transferred genes as judged by immunofluorescence of LDL receptors or by beta-galactosidase staining. These results demonstrate that adenovirus-mediated transfer of the LDL receptor gene provides an efficient way of augmenting LDL receptor gene function in the liver over the short term.