DEFECTIVE CATABOLISM AND ABNORMAL COMPOSITION OF LOW-DENSITY LIPOPROTEINS FROM MUTANT PIGS WITH HYPERCHOLESTEROLEMIA
DEFECTIVE CATABOLISM AND ABNORMAL COMPOSITION OF LOW-DENSITY LIPOPROTEINS FROM MUTANT PIGS WITH HYPERCHOLESTEROLEMIA
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DOI：
10.1021/bi00406a020
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发表时间：
1988-03-22
期刊：
影响因子：
2.9
通讯作者：
ATTIE, AD
中科院分区：
文献类型：
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作者：
CHECOVICH, WJ;FITCH, WL;ATTIE, AD
研究了一种携带与高胆固醇血症和过早动脉粥样硬化相关的特定载脂蛋白B等位基因的猪的低密度脂蛋白（LDL）的代谢和化学性质。突变体中的LDL质量显著大于对照猪（400 ± 1000）。55 mg/dL vs 103 . ±. 26 mg/dL），以及LDL胆固醇。当正常和突变LDL注入正常猪的血液中时，突变LDL的部分分解率（FCR）比对照LDL低约30%。在突变型猪中，突变型和对照LDL的平均FCR相似，尽管它们远低于在正常猪中观察到的相应FCR。LDL颗粒的密度分布在对照组和突变猪中不同;峰值LDL漂浮率从Sfo = 5.3 ±-. 1.9在控制到一个更浮力7.4 .+-。0.5在变种人身上突变体中LDL的升高仅限于最具浮力的LDL亚种。相对于对照组中密度和大小相似的LDL，该突变型LDL亚群富含胆固醇酯（47% vs 37%），甘油三酯耗尽。较致密的LDL亚群的脂质组成（ρ. > 1.043 μ g/mL）在突变体和对照中相似。我们的结论是，这些突变猪的高胆固醇血症是由缺陷的LDL催化剂。富含胆固醇酯的LDL亚种漂浮在血浆中，可能加速了这些动物的动脉粥样硬化形成。
Metabolic and chemical properties of low-density lipoproteins (LDLs) were studied in a strain of pigs carrying a specific apo-B allele associated with hypercholesterolemia and premature atherosclerosis. LDL mass was significantly greater in mutant than in control pigs (400 .+-. 55 mg/dL vs 103 .+-. 26 mg/dL), as was LDL cholesterol. When normal and mutant LDLs were injected into the bloodstream of normal pigs, the fractional catabolic rate (FCR) of mutant LDL was about 30% lower than that of control LDL. In mutant pigs, the mean FCR of mutant and control LDL were similar, although they were much lower than the corresponding FCRs observed in normal pigs. The density profile of LDL particles differed in control and mutant pigs; the peak LDL flotation rate was shifted from Sfo = 5.3 .+-. 1.9 in controls to a more buoyant 7.4 .+-. 0.5 in mutants. The elevation of LDL in the mutants was restricted to the most buoyant LDL subspecies. This subpopulation of mutant LDL was enriched with cholesteryl ester (47% vs 37%) and depleted of triglyceride, relative to LDL of similar density and size in controls. The lipid compositions of the denser LDL subpopulation (.rho. > 1.043 g/mL) were similar in mutants and controls. We conclude that the hypercholesterolemia of these mutant pigs is accounted for by defective catabolism of LDL. The buoyant cholesterol ester enriched LDL subspecies that accumulate in plasma may contribute to the accelerated atherogenesis that occurs in these animals.