2001 Fiscal Year Final Research Report Summary
FUNCTIONAL ROLE OF LIPOPROTEIN LIPASE IN ATHEROGENESIS - A STUDY ON TRANSGENIC RABBITS EXPRESSING HUMAN LIPOPROTEIN LIPASE
| 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)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | apoproteins / metabolism / hypercholesterolemia / atherosclerosis / HDL / transgenic rahbit / transgene / lipoproteins |
|---|
| 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.
|
-
[Publications] Ichikawa, T., Unoki, H., Sun, H., Shimoyamada, H., Shikama, T., Watanabe, T., Fan, J.: "Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits"Am J. Pathol.. 160. 227-236 (2002)
Description
「研究成果報告書概要(和文)」より
-
-
-
-
[Publications] Wu, L., Tanimoto, A., Murata, Y., Fan, J., Sasaguri, Y., Watanabe: "Induction of human metalloproteomase-12 gene transcritional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells"Biochem. Biophys. Res. Commun.. 285. 300-307 (2001)
Description
「研究成果報告書概要(和文)」より
-
-
[Publications] Ichikawa,T., Unoki, H., Sun, H., Shimbyamada, H., Shikama, T., Watanabe, T., Fan, J.: "Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits"Am. J. Pathol.. 160. 227-236 (2002)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Fan, J., Unoki, H., Kqjima, N., Sun, H., Shimoyamada, H., Deng, H., Yamada, N., Watanabe, T.: "Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis"J. Biol. Chem.. 276. 40071-40079 (2001)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Wu, L., Tanimoto, A., Murata, Y., Fan, J., Sasaguri, Y., Watanabe, T: "Induction of human metalloproteinase-12 gene transcritional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells"Biochem. Biophys. Res. Gommun.. 285. 300-307 (2001)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Fan, J., Shimoyamada, H., Sun, H., Marcovina, S., Honda, K., Watanabe, T.: "Transgenic rabbits expressing human apolipoprotein(a) develop enhanced atherosclerotic lesions in response to a cholesterol-rich diet"Arteiioscl. Thromb. Vascul Biol.. 21. 88-94 (2001)
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Publications] Fan, J. Challah, M., Shimoyamada, H., Shiomi, M., Marcovina, S., Watanabe, T.: "Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein(a)"J. Lipid Res.. 41(6). 1004-1012 (2000)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Araki, A., Fan, J., Challah, M., Bensadound, A., Yamada, N., Watanabe, T.: "Human lipoprotein lipase transgenic rabbits"Cytotechnology. 31. 1-7 (2000)
Description
「研究成果報告書概要(欧文)」より
-
