DISTRIBUTION OF OXIDATION SPECIFIC LIPID-PROTEIN ADDUCTS AND APOLIPOPROTEIN-B IN ATHEROSCLEROTIC LESIONS OF VARYING SEVERITY FROM WHHL RABBITS
DISTRIBUTION OF OXIDATION SPECIFIC LIPID-PROTEIN ADDUCTS AND APOLIPOPROTEIN-B IN ATHEROSCLEROTIC LESIONS OF VARYING SEVERITY FROM WHHL RABBITS
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DOI：
10.1161/01.atv.10.3.336
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发表时间：
1990-05-01
期刊：
影响因子：
--
通讯作者：
WITZTUM, JL
中科院分区：
文献类型：
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作者：
ROSENFELD, ME;PALINSKI, W;WITZTUM, JL
使用针对自体丙二醛缀合低密度脂蛋白 (MDA-LDL)、4-羟基壬烯醛缀合 LDL (4-HNE-LDL) 和 LDL 铜氧化产生的脱辅基蛋白 B 的蛋白片段以及抗脱辅基蛋白 B 的抗体产生的抗血清和单克隆抗体 对渡边遗传性高脂血症兔的不同严重程度的动脉粥样硬化病变进行免疫染色。在富含巨噬细胞的脂肪条纹和过渡性病变中，所有识别氧化特异性表位的抗体主要表现出颗粒和环形模式的细胞相关染色。这与识别脱辅基蛋白 B 的抗体获得的有限的细胞外弥散染色形成鲜明对比。在含有细胞数量减少的区域的更晚期病变中，针对氧化特异性表位的抗体的细胞外弥散染色增加，并与脱辅基蛋白 B 共定位。此外，存在与坏死核心相关的环形染色模式以及内膜和内膜的染色增加。 内侧平滑肌细胞。我们将这些数据解释为表明在富含巨噬细胞的病变区域，低密度脂蛋白被氧化并被细胞吸收。在相对缺乏巨噬细胞的更晚期病变中，天然和氧化的低密度脂蛋白，以及死亡和腐烂细胞释放的氧化产物，都被困在基质中，超出了那些能够积累氧化低密度脂蛋白的细胞的范围。
Antisera and monoclonal antibodies generated against autologous malondialdehyde-conjugated low density lipoprotein (MDA-LDL), 4-hydroxynonenal conjugated LDL (4-HNE-LDL), and the protein fragments of apoprotein B resulting from the copper oxidation of LDL, as well as antibodies against apoprotein B, were used to immunostain atherosclerotic lesions of varying severity from Watanabe heritable hyperlipemic rabbits. In macrophage-rich fatty streaks and transitional lesions, all of the antibodies recognizing oxidation specific epitopes exhibited predominantly cell-associated staining in particulate and annular patterns. This is in contrast to the limited, extracellular, diffuse staining obtained with the antibodies recognizing apoprotein B. In more advanced lesions containing areas with reduced numbers of cells, there was increased extracellular, diffuse staining with the antibodies against oxidation specific epitopes and co-localization with apoprotein B. In addition, there were annular staining patterns associated with the necrotic core and increased staining of intimal and medial smooth muscle cells. We interpret these data as suggesting that in areas of lesions rich in macrophages, LDL is oxidized and taken up by the cells. In more advanced lesions that are relatively devoid of macrophages, both native and oxidized LDL, as well as oxidation products released from dead and decaying cells, are trapped in the matrix, out of reach of those cells capable of accumulating oxidized LDL.