2006 Fiscal Year Final Research Report Summary
Research of the role of endothelial lipase in the pathogenesis of diabetic dyslipidemia and atherosclerosis
| Project/Area Number |
17590735
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
HIRATA Ken-ichi Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20283880)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Tatsuro Kobe University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (00379413)
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| Project Period (FY) |
2005 – 2006
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| Keywords | lipoprotein / atherosclerosis / inflammation / endothelial cell / cytokine / knockout mouse / diabetes / metabolic syndrome |
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| Research Abstract |
Pharmacological interventions to raise HDL-cholesterol (HDL-C) are currently of considerable interest in atherogenic dyslipidemia in type 2 diabetes and metabolic syndrome. We have identified endothelial lipase (EL), a new member of the lipoprotein lipase gene family, plays a central role in HDL metabolism. To explore the role of EL in HDL metabolism and atherosclerosis we analyzed EL knockout mice. EL expression correlates inversely with circulating HDL-C levels in genetic mouse models. In EL knockout mice, acute inflammatory reaction by LPS injection did not affects the HDL-C levels, although HDL-C was reduced by LPS injection in control wild type mice. Thus, upregulation of EL may account for the reduced HDL-C in systemic inflammation. These results suggest that EL may constitute to a new mechanism that causes the low HDL-C levels in metabolic syndrome and type 2 diabetes. We also established ELISA system to measure plasma EL concentration and analyzed single-nucleotide polymorphisms (SNPs) at the EL locus in human studies. Plasma EL concentration was negatively correlated with HDL-C, although plasma EL concentration was not correlated with LDL-C and triglyceride level. Further, human SNPs (584C/T) at the EL locus were linked to the pathogenesis of acute myocardial infarction. In conclusion, EL plays an important role in dyslipidemia and atherosclerosis in metabolic syndrome and can be a novel therapeutic target for raising the HDL-C levels and preventing atherosclerosis.
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