| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Atherosclerotic vascular disease frequently occurs in uremic patients receiving long-term hemodialysis (HD) and is the leading cause of death in these patients. Prominent characteristics of lipid abnormalities in HD patients is a decreased level of high density lipoprotein cholesterol and an increase in intermediate density lipoprotein (IDL) particle number. However, the exact mechanism for the decreased HDL cholesterol and increased IDL level remains unclear. In this kinetic study using stable isotope as a tracer, we wish to investigate apolipoprotein metabolism in 5 HD patients. 2H3-leucine was administered by a primed-constant infusion for 12 hrs and blood samples were collected up to 48 hrs. Tracer/tracee ratios of apoB-100 in very low density lipoprotein, IDL, low density lipoprotein and those of apoAI and AII in HDL were measured by gas-chromatography mass spectrometer, then integrated into a multicompartmental model to determine kinetic parameters. Although fractional catabolic rates (FCR) were, in general, decreased in HD patients, it was IDL apoB-100 showing the most profound decrease (70% decrease as compared to control subjects), resulting in the increased IDL apoB levels.
VLDL and LDL ApoB levels remained normal due to an accompanying decrease in production rate. FCR of apoAI and apoA-II were similar to controls, whereas production rate of AII was decreased (p=0.05). In conclusions, these findings demonstrated, in vivo, that delayed catabolism of IDL apoB-100 and decreased production of apoA-II are main underlying defects leading to IDL accumulation and decreased HDL in HD patients.
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