| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
The aim of this project is to elucidate the physiological and pathological roles of apo CI in lipid metabolism. We established the sensitive ELISA system for the measurement of human apo CI.We have submitted the manuscript containing the methodology of this assay. Using this assay we measured apo CI, CIII, and E concentrations in VLDL and IDL in diabetic patients with various degree of diabetic nephropathy. We found that VLDL-apo CI and IDL-apo CI levels are specifically increased in patients with overt-diabetic nephropathy, and these levels are closely associated with particle number (apo B) of VLDL or IDL, independently of apo CIII.In addition, we found that uremic patients with diabetic nephropathy had higher levels of apo CI and CIII, whereas nondiabetic uremic patients only had higher apo CIII level. On the other hand, we found that VLDL-apo CI level is increased in patients with coronary heart disease (CHD) and this increment is powerful determinant for CHD event, independently o
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f other risk markers. Our results suggest that VLDL-apo CI is an important CHD risk for patients with diabetic nephropathy.
In Human apo CI transgenic mice, we confirmed mild hyperlipidemia in these mice. We tried to mate between the apo CI transgenic mice and apo CIII-null mice to elucidate an independent role of apo CI in developing hyperlipidemia. Unfortunately, we could not obtain apo CI transgenic mice with apo CIII deficiency. However, we found by chance that apo CIII plays an important role in VLDL production ; i.e. VLDL-TG secretion rate is doubled in apo CIII-null mice. Since these mice have lower TG level, the lack of apo CIII would substantially stimulate VLDL removal. In addition, we found an important role of apo CIII in development of diabetic hyperlipidemia ; Streptozotocin injection causes diabetes in mice, and TG is elevated in these mice. However, this diabetic hyperlipidemia was not developed in apo CIII-null mice, suggesting that apo CIII plays a primary role in developing diabetic hyperlipidemia. Less
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