Oral administration of an apo A-I mimetic peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol
Oral administration of an apo A-I mimetic peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol
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DOI：
10.1161/hc0302.103711
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发表时间：
2002-01-22
期刊：
影响因子：
37.8
通讯作者：
Fogelman, AM
中科院分区：
文献类型：
--
作者：
Navab, M;Anantharamaiah, GM;Fogelman, AM
当将由D-或L-氨基酸合成的载脂蛋白A-I模拟肽口服给LDL受体缺失小鼠时，只有由D-氨基酸合成的肽在循环中是稳定的，并且增强了HDL保护LDL免受氧化的能力。由L-氨基酸合成的肽迅速降解并随尿排出。当一种由D-氨基酸合成的肽（D-4F）口服给LDL受体缺失的小鼠时，病变减少了79%。当添加到apoE缺失小鼠的饮用水中时，D-4F在最低测试剂量（0.05 mg/mL）下使病变减少约75%。病变的显著减少与总血浆或HDL-胆固醇的变化无关。
When apolipoprotein A-I mimetic peptides synthesized from either D- or L-amino acids were given orally to LDL receptor-null mice, only the peptide synthesized from D-amino acids was stable in the circulation and enhanced the ability of HDL to protect LDL against oxidation. The peptide synthesized from L-amino acids was rapidly degraded and excreted in the urine. When a peptide synthesized from D-amino acids (D-4F) was administered orally to LDL receptor-null mice on a Western diet, lesions decreased by 79%. When added to the drinking water of apoE-null mice, D-4F decreased lesions by approximately 75% at the lowest dose tested (0.05 mg/mL), The marked reduction in lesions occurred independent of changes in total plasma or HDL-cholesterol.