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2016 Fiscal Year Final Research Report

Involvement of the type of PCSK9 in familial hypercholesterolemia, obesity and diabetes

Research Project

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Project/Area Number 15K19038
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionNational Cardiovascular Center Research Institute

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)

Project Period (FY) 2015-04-01 – 2017-03-31
KeywordsPCSK9 / 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
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.

Free Research Field

分子生物学

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Published: 2018-03-22  

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