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APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA

APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA
CETP 缺乏和高α脂蛋白血症中的载脂蛋白代谢
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

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中文摘要
翻译
胆固醇酯转移蛋白(CETP)转移脂质如
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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APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA
APOLIPOPROTEIN METABOLISM IN CETP DEFICIENCY AND HYPERALPHALIPOPROTEINEMIA
HDL METABOLISM IN HYPOALPHALIPOPROTEINEMIA
METABOLISM OF HDL APOLIPOPROTEINS IN NORMAL & HYPOALPHALIPOPROTEINEMIC SUBJECTS