| Project/Area Number |
15K19038
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Mika Hori 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (60598043)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | PCSK9 / 変異 / 分子型 / LDL-コレステロール / 家族性高コレステロール血症 / バリアント |
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| Outline of Final Research Achievements |
In familial hypercholesterolemia, there were no significant differences in serum lipid levels and the prevalence of coronary artery diseases (CADs) between PCSK9 V4I carriers and non-carriers without LDLR mutations. In the patients carrying LDLR mutations and aged 30 years or more, the additional PCSK9 V4I variant is linked to a significantly increased prevalence of CADs in accord with the elevation of the LDL-C level. In vitro experiments, there were no differences in the expression of LDLR and the uptake of LDL between PCSK9 V4I-expressed cells and PCSK9 WT-expressed cells. However, in a setting, the uptake of LDL was significantly decreased in PCSK9 V4I-expressed cells as compared with PCSK9 WT- expressed cells.
In addition, there was inverse correlation between ratio of furin-cleaved PCSK9 to total PCSK9 and serum APOB level in patients with hypercholesterolemia. Thus, it is suggested that the rate of mature PCSK9 to total PCSK9 is associated with high LDL-C levels.
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