Elucidating molecular mechanisms of HDL functionality
| Project/Area Number |
18K08072
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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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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Kobe University |
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Principal Investigator |
Ishida Taturo 神戸大学, 医学研究科, 特命教授 (00379413)
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| Co-Investigator(Kenkyū-buntansha) |
入野 康宏 神戸大学, 医学研究科, 医学研究員 (10415565)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 高比重リポたんぱく質（HDL） / 高比重リポ蛋白（HDL) / フィブロネクチン / がん / 高比重リポタンパク質 / 高密度リポタンパク質 |
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| Outline of Final Research Achievements |
A large amount of evidence suggests that high-density lipoprotein (HDL) has anti- atherosclerotic properties. HDL-cholesterol (HDL-C) has also been widely used as a marker of cardiovascular disease. Recently, it was reported that plasma HDL-C levels are inversely correlated with cancer risk. However, the relationship between HDL and cancer pathophysiology remains unknown.
We focused on fibronectin, an essential extracellular matrix glycoprotein, as an HDL-associated protein. Our study showed the possible mechanism by which fibronectin-containing HDL enhanced cancer cell proliferation and adhesion via the focal adhesion kinase signaling pathway. Further investigation of the roles of HDL components in tumorigenesis might provide novel insight into cancer pathophysiology.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、HDL機能が心血管疾患のリスク因子として注目を集めている。炎症を基盤とする病態ではHDL構成脂質組成が変化したり、化学的修飾を受けたりすることで、HDLの機能は低下しているがその分子機序は不明な点が多い。本研究成果は、HDL機能がどのような要因・メカニズムで影響されているかについての解明へとつながることが期待される。
一方、動脈硬化性疾患のみならず癌領域でもリポ蛋白質の代謝障害と種々の臓器の発癌との関連が示唆されているが、本研究では含有する分子によってHDLは癌の発生・進展に対しむしろ負の方向に働く可能性を示し、新たな診断・治療戦略に貢献することが期待される。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Effect of rosuvastatin and eicosapentaenoic acid on neoatherosclerosis: the LINK-IT Trial2019
Author(s)
Kuroda K, Otake H, Shinohara M, Kuroda M, Tsuda S, Toba T, Nagano Y, Toh R, Ishida T, Shinke T, Hirata KI.
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Journal Title
EuroIntervention
Volume: 15
Issue: 12
Pages: e1099-e1106
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impaired Cholesterol‐Uptake Capacity of HDL Might Promote Target‐Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation2019
Author(s)
Nagano Y, Otake H, Toba T, Kuroda K, Shinkura Y, Tahara N, Tsukiyama Y, Yanaka K, Yamamoto H, Nagasawa A, Onishi H, Sugizaki Y, Takeshige R, Harada A, Murakami K, Kiriyama M, Oshita T, Irino Y, Kawamori H, Ishida T, Toh R, Shinke T, Hirata KI.
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Journal Title
Journal of the American Heart Association
Volume: 8
Issue: 9
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, Versus Cholesterol Efflux Capacity in Association with Coronary Plaque Lipid Burden2018
Author(s)
Toshihiko Oshita, Ryuji Toh, Mitsumasa Okano, Koichi Watanabe, Yuichiro Nagano, Amane Harada, Katsuhiro Murakami, Seimi Kobayashi, Masakazu Shinohara, Tetsuya Hara, Yasuhiro Irino, Hiromasa Otake,Tatsuro Ishida, Ken-ichi Hirata.
Organizer
American Heart Association Scientific Sessions
Related Report
Int'l Joint Research
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[Presentation] Searching for modulating factor of cholesterol uptake capacity, a novel indicator for HDL functionality2018
Author(s)
Toshihiko Oshita, Ryuji Toh,Mitsumasa Okano, Shigeyasu Tsuda, Koichi Watanabe, Seimi Kobayashi, Tetsuya Hara, Masakazu Shinohara, Yasuhiro Irino, Katsuhiro Murakami, Amane Harada, Tatsuro Ishida, Ken-ichi Hirata
Organizer
第50回 日本動脈硬化学会総会・学術集会
Related Report
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