Jimi S, Uesugi N, Saku K, Itabe H, Zhang B, Arakawa K, Takebayashi S
Departments of Pathology and Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):794-801. doi: 10.1161/01.atv.19.3.794.
To clarify the causes of renal dysfunction in familial lecithin:cholesterol acyltransferase (LCAT) deficiency, kidney samples from 4 patients with LCAT deficiency (3 homozygotes and 1 heterozygote) were examined immunohistochemically. All of the patients exhibited corneal opacities, anemia, renal dysfunction, deficiencies in plasma high density lipoprotein and LCAT activity and mass, and an increase in the ratio of plasma unesterified cholesterol to esterified cholesterol. Renal lesions began with the deposition of lipidlike structures in the glomerular basement membrane, and these structures accumulated in the mesangium and capillary subendothelium. By electron microscopy, 2 types of distinctive structure were found in glomerular lesions: vacuole structures and cross-striated, membranelike structures. The plasma oxidized phosphatidylcholine (oxPC) -modified low density lipoprotein (LDL) levels in LCAT-deficient subjects were significantly (P<0.01) higher than those in controls (1.30+/-0.82 versus 0.42+/-0.32 ng/5 microg LDL, respectively), and a significant (P<0.01) difference was observed even after adjustment for confounding factors by an analysis of covariance. The patient with the highest plasma oxPC-modified LDL had the most membranelike structures in the glomeruli and showed the greatest renal deterioration from a young age. In glomerular lesions, although there was an abundance of apoB and apoE, oil red O-positive lipids, macrophages, apoA1, and malondialdehyde were scarce. OxPC was found extracellularly in glomerular lesions, and although its distribution differed from that of apolipoproteins, it was quite similar to that of phospholipids. In conclusion, these results indicate that oxPC in plasma and glomeruli is distinctive for patients with LCAT deficiency. Therefore, oxPC may be a factor in the deterioration of kidneys in patients with familial LCAT deficiency.
为阐明家族性卵磷脂胆固醇酰基转移酶（LCAT）缺乏症患者肾功能不全的病因，对4例LCAT缺乏症患者（3例纯合子和1例杂合子）的肾脏样本进行了免疫组织化学检查。所有患者均表现出角膜混浊、贫血、肾功能不全、血浆高密度脂蛋白缺乏以及LCAT活性和质量降低，同时血浆未酯化胆固醇与酯化胆固醇的比值升高。肾脏病变始于肾小球基底膜中脂样结构的沉积，这些结构在系膜和毛细血管内皮下积聚。通过电子显微镜检查，在肾小球病变中发现了两种独特的结构：空泡结构和横纹状、膜样结构。LCAT缺乏症患者血浆氧化磷脂酰胆碱（oxPC）修饰的低密度脂蛋白（LDL）水平显著高于对照组（P<0.01）（分别为1.30±0.82与0.42±0.32 ng/5μg LDL），即使在通过协方差分析对混杂因素进行校正后，仍观察到显著差异（P<0.01）。血浆oxPC修饰的LDL水平最高的患者肾小球中膜样结构最多，且从年轻时起肾脏恶化程度最大。在肾小球病变中，虽然有大量载脂蛋白B和载脂蛋白E，但油红O阳性脂质、巨噬细胞、载脂蛋白A1和丙二醛很少。在肾小球病变中，oxPC在细胞外被发现，虽然其分布与载脂蛋白不同，但与磷脂非常相似。总之，这些结果表明，血浆和肾小球中的oxPC在LCAT缺乏症患者中具有独特性。因此，oxPC可能是家族性LCAT缺乏症患者肾脏恶化的一个因素。
