Enhanced fractional catabolic rate of apo A-I and apo A-II in heterozygous subjects for apo A-IZaragoza (L144R)
Enhanced fractional catabolic rate of apo A-I and apo A-II in heterozygous subjects for apo A-IZaragoza (L144R)
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DOI：
10.1016/s0021-9150(00)00555-4
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发表时间：
2001-02-15
期刊：
影响因子：
5.3
通讯作者：
Pocovi, M
中科院分区：
文献类型：
--
作者：
Recalde, D;Velez-Carrasco, W;Pocovi, M
我们最近报道了一个新的载脂蛋白(Apo)A-I变体(apo A-I-Zaragoza L144R)，在一个西班牙家庭中，年龄和性别的高密度脂蛋白水平低于第5个百分位数，且apo A-I浓度较低。所有apo A-i-Zaragoza受试者均为杂合子，无一人有冠状动脉疾病(CAD)的证据。载脂蛋白A-I-Zaragoza携带者的平均血浆高密度脂蛋白-C、载脂蛋白A-I和载脂蛋白A-II水平低于对照组(40、60。和50%)。脂质成分分析显示，载脂蛋白A-i-Zaragoza携带者的高密度脂蛋白颗粒中高密度脂蛋白甘油三酯百分比高于对照组，而高密度脂蛋白酯化胆固醇百分比低于对照组。卵磷脂：载脂蛋白A-I-Zaragoza携带者的胆固醇酰基转移酶(LCAT)活性和胆固醇酯化率正常。对两名载脂蛋白A-I-Zaragoza杂合子携带者和6名对照受试者进行载脂蛋白A-I和载脂蛋白A-II代谢研究。[5，5，5-H-2(3)]亮氨酸和高密度脂蛋白ApoA-I和ApoA-II示踪剂/踪迹比值用气相色谱-质谱仪测定，并用SAAM II软件拟合成单指数方程。两个携带apo A-I-Zaragoza变异体的受试者的平均apo A-I部分分解代谢率(Fcr)值分别为0.470+/-0.0792和0.207+/-0.0635天(-1)，是对照组的两倍以上。ApoA-I-Zaragoza组的载脂蛋白A-I分泌率(SR)略高于对照组(分别为17.32+/-0.226和12.76+/-3.918 mg·kg~(-1)·d~(-1))。ApoA-I-Zaragoza组和正常对照组相比，ApoA-II FCR也显著升高(分别为0.366+/-0.1450天和0.171+/-0.0333天(-1))，ApoA-II SR正常(分别为2.31+/-0.517天和2.1+/-0.684 mg kg(-L)天(-1))。我们的结果表明，apo A-I-Zaragoza变异体导致了异常的高密度脂蛋白颗粒组成的杂合性，并增强了apo A-I和apo A-II的分解代谢，而对这些载脂蛋白的分泌速率和LCAT的激活没有明显的影响。(C)2001爱思唯尔爱尔兰科学有限公司。保留所有权利。
We have recently reported a new apolipoprotein (apo) A-I variant (apo A-I-Zaragoza L144R) in a Spanish family with HDL-C levels below the 5th percentile for age and sex and low apo A-I concentrations. All the apo A-I-Zaragoza subjects were heterozygous and none of them showed evidence of coronary artery disease (CAD). Mean plasma HDL-C, apo A-I, and apo A-II levels were lower in apo A-I-Zaragoza carriers as compared to control subjects (40, 60. and 50%, respectively). Lipid composition analysis revealed that apo A-I-Zaragoza carriers had HDL particles with a higher percentage of HDL triglyceride and a lower percentage of HDL esterified cholesterol as compared to those of control subjects. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate of apo A-I-Zaragoza carriers were normal. Apo A-I and apo A-II metabolic studies were performed on two heterozygous apo A-I-Zaragoza carriers and on six control subjects. We used a primed constant infusion of [5,5,5-H-2(3)]leucine and HDL apo A-I and apo A-II tracer/tracee ratios were determined by gas chromatography mass spectrometry and fitted to a monoexponential equation using SAAM II software. Both subjects carrying apo A-I-Zaragoza variant showed mean apo A-I fractional catabolic rate (FCR) values more than two-fold higher than mean FCR values of their controls (0.470+/-0.0792 vs. 0.207+/-0.0635 day(-1), respectively). Apo A-I secretion rate (SR) of apo A-I-Zaragoza subjects was slightly increased compared with controls (17.32+/-0.226 vs. 12.76+/-3.918 mg kg(-1) day(-1), respectively). Apo A-II FCR was also markedly elevated in both subjects with apo A-I-Zaragoza when compared with controls (0.366 +/- 0.1450 vs. 0.171+/-0.0333 day(-1), respectively) and apo A-II SR was normal (2.31+/-0.517 vs. 2.1+/-0.684 mg kg(-l) day(-1), respectively). Our results show that the apo A-I-Zaragoza variant results in heterozygosis in abnormal HDL particle composition and in enhanced catabolism of apo A-I and apo A-II without affecting significantly the secretion rates of these apolipoproteins and the LCAT activation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.