In vivo evaluation of lipoprotein cholesterol ester metabolism in patients with liver disease

In vivo evaluation of lipoprotein cholesterol ester metabolism in patients with liver disease
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肝病患者脂蛋白胆固醇酯代谢的体内评价

DOI:
10.1016/0016-5085(83)90431-6
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发表时间:
1983
期刊:
影响因子:
29.4
通讯作者:
L. Swell
L. Swell
中科院分区:
医学1区
文献类型:
--
作者:
P. Monroe;Z. Vlahcevic;L. Swell

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与11名正常人相比,15名肝病患者的血浆卵磷脂胆固醇酰基转移酶活性(62%)和胆固醇酯浓度(46%)均显著降低。胆固醇酯浓度的变化仅限于高密度脂蛋白和极低密度脂蛋白;低密度脂蛋白组分没有显着改变。对血浆卵磷脂和脂蛋白胆固醇酯的检查显示,肝病患者的饱和和单不饱和脂肪酸含量明显高于正常人,亚油酸含量低于正常人。对2例正常人和2例严重胆固醇血症患者同时给予[~(14)C]甲羟戊酸和游离[~3H]胆固醇标记的高密度脂蛋白进行了脂蛋白胆固醇酯动力学研究。脂蛋白胆固醇酯模型的开发,适合两者的3H和14 C数据。高密度脂蛋白胆固醇酯的前体是游离胆固醇和低密度脂蛋白胆固醇酯;两组受试者中的分布模式均有利于低密度脂蛋白胆固醇酯(正常人为71%,哮喘患者为88%)。高密度脂蛋白胆固醇酯的周转率在两组受试者中相似,但在阿尔茨海默病患者中游离胆固醇流入高密度脂蛋白胆固醇酯的流量大大减少。在胆固醇血症患者中,这仅占总脂蛋白胆固醇酯合成量的9%和12%;在正常人中,这一数值分别为68%和74%。极低密度脂蛋白胆固醇酯的周转在糖尿病患者中被大大抑制,它们的前体来源是高密度脂蛋白胆固醇酯和组织游离胆固醇。低密度脂蛋白胆固醇酯前体是极低密度脂蛋白、低密度脂蛋白和组织游离胆固醇。在胆固醇血症患者中,更大比例(78%和88%)的低密度脂蛋白胆固醇酯来自游离胆固醇。此外,这些酯的周转率降低,在阿尔茨海默病患者。本报告提供的证据表明,胆固醇血症患者的血浆脂蛋白胆固醇酯大部分来自酰基辅酶A-胆固醇酰基转移酶游离胆固醇组织来源,最有可能是肠道。相比之下,在正常受试者中,对血浆酯的主要贡献是通过将新形成的胆固醇酯引入高密度脂蛋白组分中。
Fifteen patients with liver disease were found to have marked reductions in both plasma lecithincholesterol acyltransferase activity (62%) and cholesterol ester concentration (46%) when compared with 11 normal subjects. The changes in cholesterol ester concentration were confined to high-density lipoprotein and very-low-density lipoprotein; the low-density lipoprotein fraction was not significantly altered. Examination of the plasma lecithin and lipoprotein cholesterol esters revealed that patients with liver disease had significantly greater amounts of saturated and monounsaturated fatty acids and less linoleic acid than normal subjects. Lipoprotein cholesterol ester kinetic studies were carried out in 2 normal subjects and 2 severely cirrhotic patients who simultaneously received [14C]mevalonic acid and high-density lipoprotein labeled with free [3H]cholesterol. A lipoprotein cholesterol ester model was developed that fit both the3H and14C data. The precursors of high-density lipoprotein cholesterol esters were free cholesterol and low-density lipoprotein cholesterol esters; the distribution pattern was in favor of low-density lipoprotein cholesterol esters in both groups of subjects (71% for normals and 88% for cirrhotics). The turnover of high-density lipoprotein cholesterol esters was similar in both groups of subjects, but the flux of free cholesterol into high-density lipoprotein cholesterol esters was greatly reduced in the cirrhotic patients. In cirrhotic patients, this represented only 9% and 12% of the total lipoprotein cholesterol ester synthesized; in the normal subjects, the values were 68% and 74%. The turnover of very-low-density lipoprotein cholesterol esters was greatly suppressed in the cirrhotic patients, and their precursor sources were high-density lipoprotein cholesterol esters and tissue free cholesterol. The low-density lipoprotein cholesterol ester precursors were very-low-density lipoprotein, low-density lipoprotein, and tissue free cholesterol. In the cirrhotic patients, much greater proportions (78% and 88%) of low-density lipoprotein cholesterol ester were derived from free cholesterol. Also, the turnover rates of these esters were reduced in the cirrhotic patients. The present report has provided evidence that cirrhotic patients derive most of their plasma lipoprotein cholesterol esters from an acyl-CoA-cholesterol acyltransferase free-cholesterol tissue source—most likely the intestine. By contrast, in normal subjects, the major contribution to plasma esters is via the introduction of newly formed cholesterol esters into the high-density lipoprotein fraction.
在模拟细胞内胆固醇酯化过程中,培养的大鼠肝细胞分泌富含胆固醇酯的极低密度脂蛋白。
DOI: --
发表时间: 1980
影响因子: 6.5
作者:
Drevon,CA;Engelhorn,SC;Steinberg,D
通讯作者: Steinberg,D
培养猪肝细胞中同源低密度脂蛋白的受体介导的分解代谢。
DOI: --
发表时间: 1981
期刊: The Journal of biological chemistry
影响因子: --
作者:
Pangburn,SH;Newton,RS;Chang,CM;Weinstein,DB;Steinberg,D
通讯作者: Steinberg,D