2010 Fiscal Year Final Research Report
Mechanisms for the development of atherosclerosis with low HDL levels and of fatty liver
| Project/Area Number |
20590072
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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 |
Biological pharmacy
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
AKIBA Satoshi Kyoto Pharmaceutical University, 薬学部, 教授 (70231826)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 生化学 |
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| Research Abstract |
Metabolic syndrome with local inflammation progresses to atherosclerosis and non-alcoholic fatty liver disease (NAFLD). The present study examined the possible involvement of group IVA phospholipase A_2 (IVA-PLA_2), which catalyzes the first step of the biosynthesis of inflammatory lipid mediators, in the development of (1) atherosclerosis and (2) NAFLD using IVA-PLA_2-knockout (KO) mice.
(1) Wild-type mice on high-fat diets developed the formation of atherosclerotic lesions in the aortic root with low serum levels of HDL-cholesterol (HDL-C), compared with wild-type mice fed normal diets. IVA-PLA_2-KO mice on high-fat diets exhibited resistance to the formation of lesions even with low serum levels of HDL-C. These findings indicate that a deficiency of IVA-PLA_2 alleviates the high-fat diet-induced formation of atherosclerotic lesions without improving dyslipidemia.
(2) Wild-type mice on high-fat diets developed fatty liver, compared with wild-type mice fed normal diets. However, these high-fat diet-induced alterations were markedly decreased in IVA-PLA_2-KO mice. Furthermore, high-fat diets induced liver fibrosis with the expression of collagen type I A_2 and transforming growth factor-β mRNA in the liver of wild-type mice but not IVA-PLA_2-KO mice. These findings indicate that a deficiency of IVA-PLA_2 protected mice against the high-fat diet-induced development of NAFLD with fibrosis.
The present results suggest the possible involvement of IVA-PLA_2 in development of atherosclerosis and NAFLD.
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