| Project/Area Number |
07457051
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kyushu University |
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Principal Investigator |
NAKASHIMA Yutaka Kyushu Univ, Fac Medicine, Associate Prof., 医学部, 助教授 (50135349)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kazunori Kyushu Univ, Fac Medicine, Associate Prof., 医学部, 講師 (50217668)
KONO Shinji Kyushu Univ, School Health Sci, Associate Prof., 医療技術短期大学部, 助教授 (20225379)
SUEISHI Katsuo Kyushu Univ, Fac Medicine, Prof., 医学部, 教授 (70108710)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | atherosclerosis / ApoE-deficient mouse / VCAM-1 / ICAM-1 / PECAM-1 / in situ immnocytochemistry / monocyte / shear stress / apollipoproteinE欠損マウス / E-selectin / P-selectin / in situ免疫染色 / 接着因子 / 遺伝子欠損マウス / in situ免疫法 |
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| Research Abstract |
Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in the formation of lesions of atherosclerosis. This localized accumulation of leukocytes is a multistep process in which the endothelium remains intact and may regulate leukocyte recruitment by expressing specific adhesion molecules. To examine the relationship of adhesion molecule expression to initiation factors and the sites of lesion formation, we have analyzed the expression of VCAM-1, ICAM-1, and PECAM-1 en face on the aortic endothelium of control mice and homozygous apolipoprotein E-deficient mice that develop complex lesions of atherosclerosis similar to those in humans. In control mice, VCAM-1 staining is weak and limited to sites of altered blood flow. In contrast, in the ApoE-deficient mice, VCAM-1 appears to be localized over the surface of groups of endothelial cells in lesion-prone sites. Its expression precedes lesion formation, and increased expression above control levels appears to correlate with extent of exposure to plasma cholesterol. Although ICAM-1 is the most prominent adhesion molecule in lesion-prone sites, its expression appears to be independent of plasma cholesterol levels and is upregulated in both ApoE -/- and control mice. At lesion-prone sites asociated with altered blood flow, ICAM-1 is located over the surface of each endothelial cell and on microvilli, whereas it is confined to the cell periphery in nonlesion-prone sites. PECAM-1 is localized at the cell periphery throughout the aorta, and its expression does not appear to be regulated. Thus, the levels, localization, and characteristics of expression of VCAM-1, ICAM-1, and PECAM-1 appear to be differentially regulated. Upregulation of VCAM-1 and ICAM-1 is associated with sites of lesion formation.
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