Ravalli S, Marboe C C, D'Agati V D, Michler R E, Sigal E, Cannon P J
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Arterioscler Thromb Vasc Biol. 1995 Mar;15(3):340-8. doi: 10.1161/01.atv.15.3.340.
15-Lipoxygenase (15-LO) catalyzes the oxygenation of arachidonic and linoleic acids and has been implicated in the oxidative modification of low-density lipoproteins (LDL). 15-LO mRNA and protein have previously been demonstrated in macrophages of rabbit and human atherosclerotic lesions. The purpose of this study was to investigate whether 15-LO is also present in the accelerated form of coronary artery disease that can complicate cardiac transplantation (TCAD). Immunohistochemical analysis of coronary arteries with TCAD was carried out by using a rabbit polyclonal antibody raised against human recombinant 15-LO and an avidin-biotin-immunoperoxidase system. Normal coronary and pulmonary arteries showed no immunostaining for 15-LO. Two different types of TCAD were observed. One type consisted of concentric intimal proliferation of smooth muscle cells, without lipid or calcium deposits. No immunoreactivity for 15-LO was present in these lesions. The second type of graft arteriosclerosis consisted of complex atheromatous lesions, containing myointimal cells, lipid-laden foam cells, fragmented internal elastic laminae, and calcifications. 15-LO immunostaining of myointimal cells, lipid-laden foam cells, and endothelial cells was consistently present in these atheromatous lesions. The majority of the myointimal and foam cells positive for 15-LO were recognized by antisera to alpha-smooth muscle actin; the others were identified as macrophages. The results indicate that 15-LO expression is present in endothelial, myointimal, and foam cells in complex atheromatous lesions of TCAD, and suggest that 15-LO may play a role in the pathogenesis of this form of the disease.
15-脂氧合酶（15-LO）催化花生四烯酸和亚油酸的氧化，并且与低密度脂蛋白（LDL）的氧化修饰有关。先前已在兔和人动脉粥样硬化病变的巨噬细胞中证实了15-LO信使核糖核酸（mRNA）和蛋白质的存在。本研究的目的是调查15-LO是否也存在于可使心脏移植（TCAD）复杂化的冠状动脉疾病的加速形式中。使用针对人重组15-LO产生的兔多克隆抗体和抗生物素蛋白-生物素-免疫过氧化物酶系统对患有TCAD的冠状动脉进行免疫组织化学分析。正常冠状动脉和肺动脉对15-LO无免疫染色。观察到两种不同类型的TCAD。一种类型由平滑肌细胞的同心内膜增生组成，无脂质或钙沉积。这些病变中不存在15-LO的免疫反应性。第二种类型的移植动脉硬化由复杂的动脉粥样硬化病变组成，包含肌内膜细胞、富含脂质的泡沫细胞、破碎的内弹性膜和钙化。在这些动脉粥样硬化病变中始终存在肌内膜细胞、富含脂质的泡沫细胞和内皮细胞的15-LO免疫染色。大多数对15-LO呈阳性的肌内膜细胞和泡沫细胞可被抗α-平滑肌肌动蛋白抗血清识别；其他细胞则被鉴定为巨噬细胞。结果表明，15-LO表达存在于TCAD复杂动脉粥样硬化病变的内皮细胞、肌内膜细胞和泡沫细胞中，并提示15-LO可能在这种疾病形式的发病机制中起作用。
