Patsch W, Witztum J L, Ostlund R, Schonfeld G
J Clin Invest. 1980 Jul;66(1):123-9. doi: 10.1172/JCI109825.
In this report we compare the cord blood lipoproteins of a newborn boy homozygote who has low density lipoprotein (LDL) receptor-defective familial hypercholesterolemia (FH) with the lipoproteins from cord blood of normal newborns. Plasma LDL-cholesterol and apoprotein (Apo)B were 612 and 233 mg/dl (vs. 31+/-16 and 24+/-12 mg/dl, respectively, for normals, n = 21). LDL-cholesterol/ApoB ratio was 2.6 vs. 1.4+/-0.5. Levels of ApoA-I, ApoA-II, and HDL-cholesterol were similar to normal cord plasma. Thus, the lipoprotein abnormality is apparent at birth and is definitely present in LDL. Abnormalities in other lipoprotein, lipid, and in plasma apoprotein levels were not detected. On zonal ultracentrifugation, FH LDL was comprised of two populations (LDL(a) and LDL(b)), both faster floating than normal cord LDL (LDL(c)). This difference was due to the larger diameters of the particles on electron microscopy (LDL(a) = 276A+/-32 and LDL(b) = 260A+/-38 vs. LDL(c) = 237A+/-26, n = 200 each, mean+/-1 SD), and their higher contents of lipids relative to protein (86 and 82% vs. 74%, LDL(a), LDL(b), and LDL(c), respectively). More than 94% of the protein in both the FH and the normal preparations consisted of ApoB. FH LDL were more effective than control LDL in competing with (125)I-LDL (adult) for limiting amounts of anti-LDL antibodies in radioimmunoassay. FH LDL also competed more effectively for binding to LDL receptors on cultured fibroblasts at 4 degrees C, and FH LDL also delivered more cholesterol into the cells. Cells grown in lipoprotein-deficient serum contained 44+/-2 mug cholesterol/mg cell protein, incubation of cells for 18 h at 37 degrees C in 5 mug/ml FH LDL (protein) or in normal LDL raised cellular cholesterol levels to 75+/-2 and 60+/-2 mug/mg, respectively.LDL isolated from the FH patient's plasma at 6 mo of age and from his brother's plasma (a 5-yr-old boy FH homozygote) were similar to LDL isolated from normolipemic subjects in flotation properties, chemical composition, and immunochemical and cell reactivity. The fact that differences between normal cord LDL and FH cord LDL were present at birth, but that the differences between control and FH LDL were no longer present postnatally suggests that the altered immunologic and cell interactive properties of FH cord LDL were probably related to its unusually high contents of core lipids.
在本报告中，我们比较了一名患有低密度脂蛋白（LDL）受体缺陷型家族性高胆固醇血症（FH）的纯合子新生男婴的脐血脂蛋白与正常新生儿脐血中的脂蛋白。血浆LDL胆固醇和载脂蛋白（Apo）B分别为612和233mg/dl（相比之下，正常人为31±16和24±12mg/dl，n = 21）。LDL胆固醇/ApoB比值为2.6，而正常人为1.4±0.5。ApoA-I、ApoA-II和HDL胆固醇水平与正常脐血浆相似。因此，脂蛋白异常在出生时就很明显，且肯定存在于LDL中。未检测到其他脂蛋白、脂质及血浆载脂蛋白水平的异常。在区带超速离心时，FH LDL由两个群体组成（LDL(a)和LDL(b)），两者漂浮速度均比正常脐LDL（LDL(c)）快。这种差异是由于电子显微镜下颗粒直径更大（LDL(a) = 276A±32，LDL(b) = 260A±38，而LDL(c) = 237A±26，每组n = 200，均值±1标准差），且相对于蛋白质它们的脂质含量更高（分别为86%、82%和74%，LDL(a)、LDL(b)和LDL(c)）。FH和正常制剂中超过94%的蛋白质由ApoB组成。在放射免疫分析中，FH LDL在与（125）I-LDL（成人）竞争有限量的抗LDL抗体方面比对照LDL更有效。在4℃时，FH LDL与培养的成纤维细胞上的LDL受体结合也更有效，并且FH LDL向细胞内输送的胆固醇更多。在缺乏脂蛋白的血清中生长的细胞含有44±2μg胆固醇/mg细胞蛋白，在37℃下将细胞与5μg/ml FH LDL（蛋白质）或正常LDL孵育18小时后，细胞胆固醇水平分别升至75±2和60±2μg/mg。从6个月大的FH患者血浆及其兄弟（一名5岁的FH纯合子男孩）血浆中分离的LDL，在漂浮特性、化学成分、免疫化学及细胞反应性方面与从血脂正常的受试者中分离出LDL相似。正常脐LDL与FH脐LDL在出生时存在差异，但对照LDL与FH LDL在出生后差异不再存在，这一事实表明，FH脐LDL改变的免疫和细胞相互作用特性可能与其核心脂质异常高含量有关。
