Yancey Patricia G, Asztalos Bela F, Stettler Nicolas, Piccoli David, Williams David L, Connelly Margery A, Rothblat George H
Division of Gastroenterology and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
J Lipid Res. 2004 Sep;45(9):1724-32. doi: 10.1194/jlr.M400133-JLR200. Epub 2004 Jun 21.
Alagille syndrome is associated with bile duct paucity resulting in liver disease. Patients can be divided into mildly and severely icteric groups, with both groups having altered lipoproteins. The incidence of ischemic heart disease is rare in severely cholestatic children despite increased total cholesterol and decreased high density lipoprotein cholesterol (HDL-C). The present studies examine the impact of altered lipid and lipoproteins on scavenger receptor class B type I (SR-BI)- and ABCA1-mediated efflux to serum from both groups. Efflux was compared with serum from 29 patients (15 with normal plasma cholesteryl ester, 14 with low cholesteryl ester). Efflux via SR-BI and ABCA1 was studied using cell systems having either low or high expression levels of these receptors. SR-BI efflux was lower (P = 0.04) with serum from severely icteric patients (3.9 +/- 1.4%) compared with serum from mildly icteric patients (5.1 +/- 1.4%) and was positively correlated with HDL-C and its apolipoproteins. SR-BI-mediated efflux was not correlated with any particular mature HDL but was negatively correlated with small lipid-poor prebeta-1 HDL. Consistent with severely icteric patients having high prebeta-1 HDL levels, the ABCA1 efflux was significantly higher with their serum (4.8 +/- 2.2%) compared with serum from mildly icteric patients (2.0 +/- 0.6%) and was positively correlated with prebeta-1 HDL. These studies demonstrated that prebeta-1 HDL is the preferred acceptor for ABCA1 efflux, whereas many particles mediate SR-BI efflux.
阿拉吉尔综合征与胆管稀少有关，进而导致肝脏疾病。患者可分为轻度黄疸组和重度黄疸组，两组患者的脂蛋白均有改变。尽管总胆固醇升高和高密度脂蛋白胆固醇（HDL-C）降低，但重度胆汁淤积儿童患缺血性心脏病的发生率较低。本研究探讨了脂质和脂蛋白改变对两组患者清道夫受体B1型（SR-BI）和ABCA1介导的向血清外流的影响。将外流情况与29例患者（15例血浆胆固醇酯正常，14例胆固醇酯低）的血清进行比较。使用这些受体表达水平低或高的细胞系统研究通过SR-BI和ABCA1的外流。与轻度黄疸患者的血清（5.1±1.4%）相比，重度黄疸患者的血清（3.9±1.4%）通过SR-BI的外流较低（P = 0.04），且与HDL-C及其载脂蛋白呈正相关。SR-BI介导的外流与任何特定的成熟HDL均无相关性，但与小的低脂前β-1 HDL呈负相关。与重度黄疸患者前β-1 HDL水平较高一致，其血清的ABCA1外流（4.8±2.2%）显著高于轻度黄疸患者的血清（2.0±0.6%），且与前β-1 HDL呈正相关。这些研究表明，前β-1 HDL是ABCA1外流的首选受体，而许多颗粒介导SR-BI外流。
