APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA
APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA
批准号:
3779545
负责人:
D J RADER
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
apolipoproteins blood lipoprotein metabolism cholesterol esters familial hyperlipoproteinemia high density lipoproteins human middle age (35-64) human subject inborn lipid /lipoprotein disorder lipid transport low density lipoprotein receptor expression stable isotope diagnosis tissue /cell culture transport proteins very low density lipoprotein young adult human (21-34)
中文摘要
胆固醇酯转移蛋白(CETP)可转移脂类,如
含载脂蛋白B的脂蛋白中的胆固醇和甘油三酯
低密度脂蛋白)和含apoA-I的脂蛋白(高密度脂蛋白)。遗传缺陷
CETP导致低水平的apoB和低密度脂蛋白,高水平的apoA-I和高密度脂蛋白,
并被提议作为一种保护条件,防止
冠心病的发展。我们深入调查了
两例无血缘关系的CETP缺乏症患者的脂蛋白代谢
既使用稳定同位素的内源标记,也使用外源标记
标记的放射性示踪剂。我们确定了两者的分解代谢率
载脂蛋白A-I和高密度脂蛋白胆固醇显著低于正常
受试者,占他们较高的血浆水平。这表明
CETP缺乏症实际上可能会延迟胆固醇的反向转运,
高密度脂蛋白的高水平可能由不同的
机制。我们还测定了极低密度脂蛋白向低密度脂蛋白的转化率
在CETP缺乏时显著延迟,导致显著
极低密度脂蛋白转化为低密度脂蛋白前分解代谢增加。这本帐目
这些受试者的血浆载脂蛋白B和低密度脂蛋白胆固醇水平较低。
这些综合结果表明CETP的药理抑制作用
可能会延迟高密度脂蛋白的分解代谢,导致新陈代谢
将极低密度脂蛋白引导到降解途径而不是低密度脂蛋白
队形。
建立了一种定量测定血浆CETP活性的方法。
这将使我们能够详细评估CETP的影响
对高密度脂蛋白代谢的影响。正在进行的研究涉及到进一步的
CETP缺乏症载脂蛋白代谢的研究
在其他高脂蛋白血症患者中。
这些研究对象的年龄在19岁到67岁之间。56%的
受试者为女性。其中六名受试者是亚洲人。
英文摘要
The cholesterol ester transfer protein (CETP) transfers lipids such as
cholesterol and triglycerides among apoB-containing lipoproteins (VLDL,
LDL) and apoA-I-containing lipoproteins (HDL). Genetic deficiency of
CETP causes low levels of apoB and LDL and high levels of apoA-I and HDL,
and has been proposed to be a protective condition against the
development of coronary heart disease. We intensively investigated the
lipoprotein metabolism in two unrelated patients with CETP deficiency
using both endogenous labeling with stable isotopes and exogenously
labeled radiotracers. We established that the catabolic rates of both
apoA-I and HDL-cholesterol ester were substantially slower than in normal
subjects, accounting for their higher plasma levels. This suggests that
reverse cholesterol transport may actually be delayed in CETP deficiency,
and that the high levels of HDL may be protective by a different
mechanism. We also determined that the rate of conversion of VLDL to LDL
is significantly delayed in CETP deficiency, resulting in markedly
increased catabolism of VLDL before its conversion to LDL. This accounts
for the low plasma levels of apoB and LDL cholesterol in these subjects.
These combined results suggest that pharmacologic inhibition of CETP
would be likely to delay catabolism of HDL and to cause metabolic
channelling of VLDL to a degradation pathway rather than to LDL
formation.
An assay to quantitate CETP activity in the plasma has been developed.
This will permit the detailed assessment of the influence of CETP
activity on HDL metabolism. Ongoing studies involve further
investigation into the metabolism of apolipoproteins in CETP deficiency
and in other patients with hyperalphalipoproteinemia.
These studies included subjects of age 19 to 67 years. 56% of the
subjects were women. Six of the subjects were Asian.
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会议论文
APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA
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批准号:3843306
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA
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批准号:3858033
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
HDL METABOLISM IN HYPOALPHALIPOPROTEINEMIA
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批准号:3757635
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF HDL APOLIPOPROTEINS IN NORMAL & HYPOALPHALIPOPROTEINEMIC SUBJECTS
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批准号:3779541
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF LPA-I AND LPA-I--A-II IN HUMANS
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批准号:3757637
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
GENETIC REGULATION OF LP(A) METABOLISM
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批准号:3779550
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF APOA-IV IN HUMANS
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批准号:3858031
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
GENETIC REGULATION OF LPA METABOLISM
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批准号:3757642
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF LIPOPROTEIN A IN HUMANS
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批准号:3779544
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF LP(A) IN HUMANS
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批准号:3858032
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF LIPOPROTEIN A IN HUMANS
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批准号:3843305
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF APOA-IV IN HUMANS
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批准号:3843304
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位:
METABOLISM OF HDL APOLIPOPROTEINS IN NORMAL & HYPOALPHALIPOPROTEINEMIC SUBJECTS
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批准号:3843299
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:D J RADER
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依托单位: