Is there a role for 15-lipoxygenase in atherogenesis?
Is there a role for 15-lipoxygenase in atherogenesis?
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DOI：
10.1016/s0006-2952(97)00135-4
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发表时间：
1997-11-01
影响因子：
5.8
通讯作者：
Cornicelli, JA
中科院分区：
文献类型：
--
作者：
Feinmark, SJ;Cornicelli, JA
15-脂氧合酶已被认为在动脉粥样硬化形成中起作用。这种酶的作用是氧化低密度脂蛋白（LDL），使LDL成为巨噬细胞清道夫受体的配体。15-脂氧合酶和氧化的LDL在动脉粥样硬化病变中共定位;阻断脂氧合酶的抗氧化剂药物也阻断LDL的氧化和实验性动脉粥样硬化的进展。生物化学实验已经证明，脂氧合酶可以由细胞因子和/或与高胆固醇血症相关的另一种因子诱导。然而，分子生物学工作表明，单独诱导酶不足以诱导损伤形成。此外，15-脂氧合酶在动脉粥样硬化形成中的作用机制仍不清楚。酶氧化亚油酸酯产物的立体化学预测似乎与现有数据相冲突。事实上，大多数研究已经发现动脉病变中大量水平的外消旋13-羟基十八碳二烯酸（13-HODE），而不是纯化酶预期的立体化学纯13（S）-HODE。15-脂氧合酶代谢产物的产生必须发生在特定的细胞位置和疾病发展的短暂时间窗内的可能性已经讨论过。亚油酸代谢物的真正功能也可能是调节基因表达和有丝分裂发生，LDL的氧化可能起次要作用。转基因物种的出现，既发展动脉粥样硬化，要么未能表达或过表达的脂氧合酶提供了一个机会，澄清这些问题在不久的将来。(C)1997年爱思唯尔科学公司
15-Lipoxygenase has been suggested to play a role in atherogenesis. The proposed action of this enzyme is to oxidize low density lipoprotein (LDL) to the extent that LDL becomes a ligand for the macrophage scavenger receptor. 15-Lipoxygenase and oxidized LDL are co-localized in atherosclerotic lesions; antioxidant drugs that block the lipoxygenase also block oxidation of LDL and the progression of experimental atherosclerosis. Biochemical experiments have demonstrated that the lipoxygenase can be induced by cytokines and/or another factor(s) associated with hypercholesterolemia. However, molecular biological work has shown that induction of the enzyme alone is not sufficient to induce lesion formation. Furthermore, the mechanism of action of 15-lipoxygenase in atherogenesis remains unclear. Predictions of the stereochemistry of enzyme-oxidized linoleate products appear to conflict with the available data. In fact, most studies have discovered substantial levels of racemic 13-hydroxyoctadecadienoic acid (13-HODE) in arterial lesions rather than the stereochemically pure 13(S)-HODE expected from purified enzyme. The possibility that the generation of products of 15-lipoxygenase metabolism must occur in a specific cellular location and during a brief time window in the development;of the disease has been discussed. It is also possible that the true function of the linoleate metabolites is to modulate gene expression and regulate mitogenesis, and that oxidation of LDL may play a secondary role. The advent of transgenic species that both develop atherosclerosis and either fail to express or overexpress the lipoxygenase presents an opportunity to clarify some of these issues in the near future. (C) 1997 Elsevier Science Inc.