Pre-beta-very low density lipoproteins as precursors of beta-very low density lipoproteins. A model for the pathogenesis of familial dysbetalipoproteinemia (type III hyperlipoproteinemia).
Pre-beta-very low density lipoproteins as precursors of beta-very low density lipoproteins. A model for the pathogenesis of familial dysbetalipoproteinemia (type III hyperlipoproteinemia).
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前β-极低密度脂蛋白作为β-极低密度脂蛋白的前体。
DOI：
10.1172/jci113642
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Chappell,DA
中科院分区：
文献类型：
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作者：
Chappell,DA
研究了家族性脂蛋白异常血症（dysβ）受试者、载脂蛋白（apo-） E2 （E2/2表型）纯合子和E3/3表型受试者的极低密度脂蛋白（VLDL）组分的物理、化学和受体结合特性，以深入了解脂蛋白异常血症的发病机制，这是一种以血浆中存在β -VLDL为特征的疾病。与β - vldl相比，来自dys- β受试者的前β - vldl更大（27比17 × 10(6) D），甘油三酯含量更高（68比43%干重）。pre - vldl在Sf大于100浮选段中占主导地位，而β - vldl在Sf 20 ~ 60浮选段中占主导地位。由于体内脂解作用可将较大的VLDL （Sf大于100）转化为较小的、富含胆固醇酯的VLDL (Sf 20-60)，因此β -VLDL前体很可能是β -VLDL的前体。虽然在V型高脂血症E3/3受试者中未发现β - vldl，但静脉肝素化诱导了β - vldl，提示体内β - vldl前体的脂解可导致β - vldl的形成。类似地，β障碍受试者的肝素化产生更多的β - vldl，以β - vldl前为代价。正常血脂和V型高脂血症E3/3受试者的前- vldl对载脂蛋白b，E（LDL）受体的亲和力分别是dysbeta受试者的90倍和280倍。来自V型高脂血症患者的肝素诱导的β - vldl的结合亲和力比来自非β型患者的肝素诱导的β - vldl高6倍。这些数据表明E2/2受试者的β - vldl与体内脂蛋白受体的相互作用较差，降低了它们的受体介导的清除率，并增加了它们在脂溶过程中向β - vldl的转化。图片
The physical, chemical, and receptor binding properties of very low density lipoprotein (VLDL) fractions from familial dysbetalipoproteinemic (dys-beta) subjects, homozygous for apolipoprotein (apo-) E2 (E2/2 phenotype), and subjects with the E3/3 phenotype were studied to gain insights into the pathogenesis of dysbetalipoproteinemia, a disorder characterized by the presence of beta-VLDL in the plasma. Pre-beta-VLDL from dys-beta subjects were larger (27 vs. 17 x 10(6) D) and more triglyceride rich (68 vs. 43% dry weight) than beta-VLDL. Pre-beta-VLDL predominated in the Sf greater than 100 flotation fraction, whereas beta-VLDL predominated in the Sf 20-60 fraction. Because lipolysis converts large VLDL (Sf greater than 100) in vivo to smaller, more cholesteryl ester-rich VLDL (Sf 20-60), it is likely that pre-beta-VLDL are precursors of beta-VLDL. Although beta-VLDL were not found in type V hyperlipidemic E3/3 subjects, they were induced by intravenous heparinization, suggesting that lipolysis of pre-beta-VLDL in vivo can result in beta-VLDL formation. Similarly, heparinization of a dys-beta subject produced more beta-VLDL, at the expense of pre-beta-VLDL. The pre-beta-VLDL from normolipidemic and type V hyperlipidemic E3/3 subjects, respectively, had 90 and 280 times the affinity for the apo-B,E(LDL) receptor than did the pre-beta-VLDL from dys-beta subjects. Heparin-induced beta-VLDL from type V hyperlipidemic subjects had a sixfold higher binding affinity than did heparin-induced beta-VLDL from dys-beta subjects. These data suggest that pre-beta-VLDL from E2/2 subjects interact poorly with lipoprotein receptors in vivo, decreasing their receptor-mediated clearance and increasing their conversion to beta-VLDL during lipolytic processing.Images