2022 Fiscal Year Final Research Report
Roles of Lysosomal Acid Lipase in Development of Coronary Artery Disease
| Project/Area Number |
17K09859
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kanazawa University |
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Principal Investigator |
Nohara Atsushi 金沢大学, 保健学系, 研究協力員 (50313648)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Keywords | Lysosomal acid lipase / 家族性高コレステロール血症 / 冠動脈疾患 / HMG-CoA-reductase阻害薬 |
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| Outline of Final Research Achievements |
Although GWAS has reported an association between coronary disease and the LIPA gene, the actual mechanism has not been fully elucidated. Cholesterol ester storage disease (CESD) and Wolman's disease are genetic defects in Lysosomal Acid Lipase (LAL). In adults with CESD, familial hypercholesterolemia (FH) is raised as a differential disease.
We measured LAL activity in blood samples from more than 400 patients with high risk of coronary disease, including FH, and found a positive correlation between LAL activity and findings of coronary arteriosclerosis. A study before and after administration of HMG-CoA inhibitors showed significant changes in LAL activity due to statins, which may be part of the efficacy.
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| Free Research Field |
脂質異常症
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| Academic Significance and Societal Importance of the Research Achievements |
心血管疾患の多くは動脈硬化症を背景としており，脂質代謝異常は特に冠動脈疾患リスクの中核の1つである．しかし脂質代謝の理解は未だ十分に解明されているとは言い難い．本研究は遺伝学的に冠動脈疾患リスクになることが示されているが，機序が不明なままになっているLIPA遺伝子でコードされるLysosomal Acid Lipase(LAL)が，実際の患者においてどのような影響を及ぼしているのかを検討し，その一端を明らかにした．
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