Project/Area Number |
23790854
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Kobe University |
Principal Investigator |
SUN Li 神戸大学, 大学院・医学研究科, 医学研究員 (10547508)
|
Co-Investigator(Renkei-kenkyūsha) |
ISHIDA Tatsuro 神戸大学, 医学部附属病院, 准教授 (00379413)
YASUDA Tomoyuki 神戸大学, 医学部附属病院, 助教 (20457047)
|
Project Period (FY) |
2011 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 高比重リポ蛋白 / 炎症 / 脂質代謝 / 血管内皮 / リパーゼ / 動脈硬化 / 家兎 / HDL / 血管内皮リパーゼ / lipase |
Research Abstract |
Endothelial lipase (EL) regulates circulating high-density lipoprotein-cholesterol (HDL-C) levels. There is a discrepancy of EL effect in lipid profiles between mise and humans. Therefore, we investigated the effect of altered EL expression on lipid profile and HDL anti-atherogenic properties in rabbits. Adenovirus encoding human EL (AdhEL) was injected into Japanese white rabbits, which induced hEL overexpression. Consequently, serum HDL-C levels were significantly decreased, while LDL-C levels were not affected. Lipoprotein fractions isolated from humans, rabbits and mice were treated with the EL-rich medium, and measured free fatty acids liberated from the lipoprotein substrates. The hEL hydrolyzed HDL from all three species, while it hydrolyzed mouse LDL much greater than rabbit- and human-LDL. Serum paraoxonase activity, a major component of HDL anti-oxidant properties, significantly reducedin EL-overexpressing rabbits, whereas serum cholesterol efflux capacity did not change despite of the reduced HDL levels. In conclusion, Human EL reduced HDL-C and HDL anti-oxidative property in rabbits. Considering that lipid profile of rabbits resembles that of humans, alteration of EL expression or activity may improve HDLlevels and anti-oxidant properties without affecting LDL-C levels in humans.
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