1998 Fiscal Year Final Research Report Summary
Study on the role of arterial retention of lipoprotein and its regulators in the development of atheroselerosis
| Project/Area Number |
09470217
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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 |
内分泌・代謝学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ISHIBASHI Syun Tokyo University, Hospital, Assistant Professor, 医学部・附属病院, 助手 (90212919)
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| Co-Investigator(Kenkyū-buntansha) |
OSUGA Jun-ichi Tokyo University, Hospital, Attending Physician, 医学部・附属病院, 医員
HARADA Kenji Tokyo University, Hospital, Attending Physician, 医学部・附属病院, 医員
YAMADA Nobuhiro Tokyo University, Hospital, Associate Professor, 医学部・附属病院, 助教授 (40200729)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Atherosclerosis / Cholesterol / Triglyceride / Lipoprotein / Apolipoprotein / Lipoprotein lipase / Knockout / Trasgenic |
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| Research Abstract |
It has been widely accepted that development of atherosclerosis is initiated by response to injury of endothelium in arterial wall. However, no evidence of the endothelial injury was found in certain animal models of atherosclerosis associated with hyperlipoproteinemia. This lead us to the hypothesis that atherosclerosis is triggered by retention of atherogenic lipoproteins in the arterila wall. To identify factors which govern retention of apo B-containing lipoproteins, we have established lines of mutant mice : APOBEC-1 knockout mice, lipoprotein lipase (LPL) trasgenic mice, apo E trasgenic mice. Apo B-48 is eliminated by the disruption of APOBEC-1 gene. We further cross-bred these animals to the low density lipoprotein receptor (LDLR) knockout mice and apo E knockout mice and examined the atherosclerosis. There was no difference in the size of aortic lesions between mice with and without apo B-48, indicating that the atherogenic potential of apo B-100 is similar to that of apo B-48. LPL overexpression reduced atherosclerotic lesion size in the setting of the apo E deficiency. Since this effect was not accompanied by the changes in the plasma apo B levels, it is plausible that LPL on the lipoproteins is directly involved in the reduction of the arterial retention of atherogenic lipoproteins. Similarly, apo E overexpression reduced atherosclerotic lesion size in the setting of the LDLR deficiency. In this case, the changes in the plaque size were parallel to those of the plasma apo B levels. Therefore, it is unlikely that apo E regulates directly the arterial retention of atherogenic lipoproteins. In conclusion, LPL may function as a regulator of arterial retention of apo B-containing lipoproteins. Apo B isoforms and apo E do not appear to have this function.
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