| Project/Area Number |
06671002
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MATSUSHIMA Teruhiko Univ.of Tsukuba, Institute of Clinical Medicine Assist.Prof., 臨床医学系, 講師 (60199792)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | lipoprotein (a) / apolipoprotein (a) / diabetes mellitus / hemodiasysis / mRNA / transcription / interleukin-6 / insulin / lipoproteins / lipoprotein(a) / atherosclerosis / gene / diabetes mellitus / interleukin / transcription / リポ蛋白 / コレステロール / リポ蛋白(a) / アポ蛋白(a) / カニクイザル / サイトカイン |
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| Research Abstract |
Lipoprotein (a) (Lp (a) ) is known to be a strong risk factor for atherosclerotic diseases. However, the basic study for Lp (a) is behind because it is present only in man and monkeys so that suitable model has been lacking. In this study, we performed the clinical studies for hyperlipoproteinemia (a) observed in the patients with diabetes mellitus and chronic renal diseases, and analyzed the production and transcription of apolipoprotein (a) as basic studies using cynomolgus monkeys as animal model and HepG2 transfected with control region of genomic DNA of apolipoprotein as in vitro model. In patients with diabetes mellitus, serum level of Lp (a) is higher than in health subject. The serum level is correlated with the numbers of affected diabetic microangiopathic complications and with the level of HbAlc. The daily excretion of urinary C-peptide residue is incersely correlated with serum Lp (a) level, which suggests the decreased effect of insulin in diabetes is involved in the increase of Lp (a) level. In primary culture of monkey hepatocytes and transformed HepG2 cells, insulin decreased apo (a) promoter activity dose dependently in the range between 10pM and 1 microM.Increment of apo (a) promoter activity was independent from the increase of osmotic pressure and dose dependent. In the patients with chronic dialysis, both of the level of serum Lp (a) and serum IL-6 werehigher than healthy subjects, and positively correlated each other. IL-6 was found to increase the production of Lp (a) DNA transcription in the study with primary culture of monkey hepatocytes and transformed HepG2 cells. It was suggested that IL-6 is involved in the elevated level of serum Lp (a) in the patient with chronic dialysis and inflammatory diseases. It was found that TGF-betal and TNF-alpha decrease apo (a) promoter activities.
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