Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts.
Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts.
复制标题
DOI：
10.1172/jci115111
复制
发表时间：
1991-04
期刊：
影响因子：
--
通讯作者：
S. Ylä-Herttuala;M. Rosenfeld;S. Parthasarathy;E. Sigal;T. Särkioja;J. L. Witztum;D. Steinberg
中科院分区：
文献类型：
--
作者：
S. Ylä-Herttuala;M. Rosenfeld;S. Parthasarathy;E. Sigal;T. Särkioja;J. L. Witztum;D. Steinberg
氧化修饰的低密度脂蛋白(LDL)显示出几种潜在的致动脉粥样硬化特性，抑制低密度脂蛋白在兔体内的氧化可降低动脉粥样硬化病变的发展速度。体外研究表明，细胞脂氧合酶可能参与了低密度脂蛋白的氧化，我们先前已经证明在兔动脉粥样硬化病变中存在15-脂氧合酶和氧化型低密度脂蛋白。我们现在报告，氧化型低密度脂蛋白的表位也在人类脂肪条纹的巨噬细胞丰富的区域以及更晚期的人类动脉粥样硬化病变中被发现。利用原位杂交和免疫染色技术，我们还报道了15-脂氧合酶mRNA和蛋白共定位于相同的巨噬细胞富集区。此外，这些相同的病变表达丰富的乙酰低密度脂蛋白受体的mRNA，但没有检测到低密度脂蛋白受体的mRNA。我们认为，人类动脉粥样硬化的形成可能与巨噬细胞通过15-脂氧合酶介导的低密度脂蛋白氧化修饰，导致随后的巨噬细胞摄取增加有关，部分是通过乙酰低密度脂蛋白受体的方式。
Oxidatively modified low density lipoprotein (LDL) exhibits several potentially atherogenic properties, and inhibition of LDL oxidation in rabbits decreases the rate of the development of atherosclerotic lesions. In vitro studies have suggested that cellular lipoxygenases may be involved in LDL oxidation, and we have shown previously that 15-lipoxygenase and oxidized LDL are present in rabbit atherosclerotic lesions. We now report that epitopes of oxidized LDL are also found in macrophage-rich areas of human fatty streaks as well as in more advanced human atherosclerotic lesions. Using in situ hybridization and immunostaining techniques, we also report that 15-lipoxygenase mRNA and protein colocalize to the same macrophage-rich areas. Moreover, these same lesions express abundant mRNA for the acetyl LDL receptor but no detectable mRNA for the LDL receptor. We suggest that atherogenesis in human arteries may be linked to macrophage-induced oxidative modification of LDL mediated by 15-lipoxygenase, leading to subsequent enhanced macrophage uptake, partly by way of the acetyl LDL receptor.