| Project/Area Number |
11470048
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | UNVERSITY OF TSUKUBA |
|---|
Principal Investigator |
FAN Jianglin UNIVERSITY OF TSUKUBA, INSTITUTE OF BASIC MEDICAL SCIENCES, Assistant Professor, 基礎医学系, 講師 (60272192)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
UNOKI Hiroyuki UNIVERSITY OF TSUKUBA, INSTITUTE OF BASIC MEDICAL SCIENCES, RESEARCH Associate, 基礎医学系, 助手 (40323290)
井出 良浩 筑波大学, 基礎医学系, 講師 (70258606)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1999: ¥5,600,000 (Direct Cost: ¥5,600,000)
|
|---|
| Keywords | apoproteins / metabolism / hypercholesterolemia / atherosclerosis / HDL / transgenic rahbit / transgene / lipoproteins / リポ蛋白 / 動物モデル / 遺伝子導入モデル / 脂質代謝 |
|---|
| Research Abstract |
Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of TG-rich lipoprbteins. To elucidate the physiological roles of LPL in lipid and lipoprotein metabolism, we generated transgenic rabbits expressing human LPL. In post-heparinized plasma of transgenic rabbits, the human LPL protein levels were about 650 ng/ml and LPL enzymatic activity was found at levels up to 4-fold greater than that in nontransgenic littermates. Increased LPL activity in transgenic rabbits was associated with as much as 80% decrease in plasma triglycerides and 59% decrease in HDL-cholesterol. Analysis of the lipoprotein density fractions revealed that increased expression of the LPL transgene resulted in a remarkable reduction in the level of very low density lipoproteins as well as in the level of intermediate density lipoproteins. In addition, LDL cholesterol levels in transgenic rabbits were significantly increased. When transgenic rabbits were fed a cholesterol-rich diet, the development of hypercholesterolemia and aortic atherosclerosis was dramatically suppressed in transgenic rabbits. These results demonstrate that systemically increased LPL activity functions in the metabolism of all classes of lipoproteins, thereby playing a crucial role in plasma triglyceride hydrolysis and lipoprotein conversion, and that overexpression of LPL protects against diet-induced hypercholesterolemia and atherosclerosis.
|
