The influence and the mechanism of hypercholesterolemia to cerebral homeostasis
| Project/Area Number |
22590057
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
ISHII Itsuko 千葉大学, 医学部附属病院, 教授 (00202929)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 脳 / コレステロール / 血液脳関門 / 血管透過性 / 腎臓 / 動脈硬化 / 脳血液関門(BBB) / 血液脳関門(BBB) |
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| Research Abstract |
We have found that cholesterol is accumulated in a brain and renal functions reduce in mice fed a high cholesterol diet. In this research, it was aimed to clarify the mechanism of increase of the vascular permeability by hypercholesterolemia of mice fed a high cholesterol diet. In the high cholesterol fed-mice, the activity of MMP9 in blood increased intentionally. The ratio of the lymphocyte in blood decreased, and that of neutrophils statistically increased. These data suggested that the permeability of BBB might be increased by MMP9 derived from neutrophils which degrades ZO-1.When mice fed a high cholesterol diet were treated ezetimibe or cholestyramine, the blood cholesterol level, MMP9 level and the ratio of the neutrophil in blood decreased. Especially, the cholestyramine which induces bile acid excretion also recovered HDL level, inhibition of induction of BBB permeability was high, and a part of renal function was also recovered. Since we found that acrolein increased in blood of hypercholesterolemia of mice fed a high cholesterol diet, we clarify whether lipoproteins modified with acrolien induces to form foam cells from macrophages.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid, an acrolein- glutathione metabolite2012
Author(s)
Yoshida, M., Mikami, T., Higashi, K., Saiki, R., Mizoi, M., Fukuda, K., Nakamura, T., Ishii, I., Nishimura, K., Toida, T., Tomitori, H., Kashiwagi, K., and Igarashi, K.
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Journal Title
Clin. Chim.Acta
Volume: 413(7-8)
Pages: 753-9
Related Report
Peer Reviewed
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[Journal Article] Nitroxide derivatives for imaging of hypercholesterolemia-induced kidney dysfunction and assessing the effectiveness of anti-lipidemicdrugs2011
Author(s)
Tomizawa, A., Hadjidekov, G., Ishii, I., Bakalova, R., Zhelev, Z., Aoki, I., Saga, T., and Kitada, M.
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Journal Title
Mol. Pharm
Volume: 8
Pages: 1962-9
Related Report
Peer Reviewed
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[Journal Article] Carbamoyl- PROXYL-enhanced MRI detects very small disruptions in brain vascular permeability induced by dietary cholesterol2011
Author(s)
Tomizawa, A., Ishii, I., Zhelev, Z., Aoki, I., Shibata, S., Kitada, M., and Bakalova, R.
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Journal Title
Biochim. Biophys. Acta -Gen. Subjects
Volume: 1810
Pages: 1309-16
Related Report
Peer Reviewed
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[Journal Article] Nitroxide derivatives for imaging of hypercholesterolemia-induced kidney dysfunction and assessing the effectiveness of anti-lipidemic drugs2011
Author(s)
Tomizawa, A., Hadjidekov, G., Ishii, I.. Bakalova, R., Zhelev, Z., Aoki, I., Saga, T., Kitada, M.
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Journal Title
Mol.Pharm.
Volume: 8
Pages: 1962-9
Related Report
Peer Reviewed
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[Journal Article] Carbamoyl-PROXYL-enhanced MRI detects very small disruptions in brain vascular permeability induced by dietary cholesterol2011
Author(s)
Tomizawa, A., Ishii, I.. Zhelev, Z., Aoki, I., Shibata, S., Kitada, M., Bakalova, R.
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Journal Title
Biochim.Biophys.Acta-Gen.Subjects
Volume: 1810
Pages: 1309-16
Related Report
Peer Reviewed
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