Study on the role of thyroid hormones in the protection of atherosclerosis
Project/Area Number |
17H04109
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Laboratory medicine
|
Research Institution | Gunma University |
Principal Investigator |
Murakami Masami 群馬大学, 大学院医学系研究科, 教授 (30241871)
|
Co-Investigator(Kenkyū-buntansha) |
木村 孝穂 群馬大学, 大学院医学系研究科, 准教授 (90396656)
常川 勝彦 群馬大学, 医学部附属病院, 講師 (30436307)
荒木 修 群馬大学, 医学部, 非常勤講師 (80589482)
奈良 誠人 群馬大学, 医学部附属病院, 助教 (80420165)
黒沢 幸嗣 群馬大学, 医学部附属病院, 助教 (80648072)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
|
Keywords | 甲状腺 / 動脈硬化 / 脂質代謝 / トリグリセライド / リポ蛋白リパーゼ / GPIHBP1 / 甲状腺ホルモン代謝 / 一塩基多型 / 甲状腺ホルモン / 肝性トリグリセライドリパーゼ / 脱ヨード酵素 / 脂質異常 / 遺伝子解析 |
Outline of Final Research Achievements |
We developed enzyme immunoassay systems for serum HTGL and GPIHBP1, which transports LPL from the subendothelial space to the capillary lumen, where LPL hydrolyzes triglycerides. We found that free T3 positively correlated with HTGL, which suggested the significance of thyroid hormones in the regulation of lipid metabolism. High normal-range TSH concentration was shown to be associated with carotid plaque in postmenopausal women, which suggested that the slight hypothyroid state was related to arteriosclerosis. We reported a patient with hypothyroidism associated with concurrent TSH receptor mutation and type 2 iodothyronine deiodinase (D2) polymorphism, which indicated the importance of D2 in the thyroid hormone metabolism. During the process of the development of GPIHBP1 enzyme assay system using GPIHBP1 monoclonal antibodies, we discovered the patients with marked hypertriglyceridemia who had autoantibodies against GPIHBP1 which abolished the capacity of GPIHBP1 to bind LPL.
|
Academic Significance and Societal Importance of the Research Achievements |
我々は、甲状腺ホルモンの動脈硬化進展抑制作用の研究を行い、わずかな甲状腺機能低下が頸動脈硬化に関連することを見出した。脂質代謝異常の病態を解明する目的で、TGを代謝するLPLを間質腔から血管内に輸送するGPIHBP1の測定法を開発したが、その過程でGPIHBP1に対する自己抗体が存在するためにLPLによるTGの代謝が障害されて著明な高TG血症をきたすGPIHBP1自己抗体症候群を発見した。それらの症例において免疫抑制剤が治療に有効である可能性が示唆された。これまで不明であった自己免疫性高TG血症の病態を解明した独創的な研究であり、新たな脂質異常症の治療法の開発につながることが期待される。
|
Report
(4 results)
Research Products
(51 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Serum autotaxin levels are associated with Graves’ disease2019
Author(s)
Nojiri Takahiro、Kurano Makoto、Araki Osamu、Nakawatari Kazuki、Nishikawa Masako、Shimamoto Satoshi、Igarashi Koji、Kano Kuniyuki、Aoki Junken、Kihara Shinji、Murakami Masami、Yatomi Yutaka
-
Journal Title
Endocrine Journal
Volume: 66
Issue: 5
Pages: 409-422
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Lipoprotein lipase is active as a monomer2019
Author(s)
Beigneux Anne P.、Allan Christopher M.、Sandoval Norma P.、Cho Geoffrey W.、Heizer Patrick J.、Jung Rachel S.、Stanhope Kimber L.、Havel Peter J.、Birrane Gabriel、Meiyappan Muthuraman、Gill John E.、Murakami Masami、Miyashita Kazuya、Nakajima Katsuyuki、Ploug Michael、Fong Loren G.、Young Stephen G.
-
Journal Title
Proceedings of the National Academy of Sciences
Volume: 116
Issue: 13
Pages: 6319-6328
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] GPIHBP1 autoantibody syndrome during interferon β1a treatment.2019
Author(s)
Eguchi J, Miyashita K, Fukamachi I, Nakajima K, Murakami M, Kawahara Y, Yamashita T, Ohta Y, Abe K, Nakatsuka A, Mino M, Takase S, Okazaki H, Hegele RA, Ploug M, Hu X, Wada J, Young SG, Beigneux AP.
-
Journal Title
J Clin Lipidol
Volume: 13
Issue: 1
Pages: 62-69
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Association between skeletal muscle mass and serum concentrations of lipoprotein lipase, GPIHBP1, and hepatic triglyceride lipase in young Japanese men.2019
Author(s)
Matsumoto R, Tsunekawa K, Shoho Y, Yanagawa Y, Kotajima N, Matsumoto S, Araki O, Kimura T, Nakajima K, Murakami M
-
Journal Title
Lipids Health Dis.
Volume: 18
Issue: 1
Pages: 84-92
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] An automated method for measuring lipoprotein lipase and hepatic triglyceride lipase activities in post-heparin plasma.2018
Author(s)
Nakajima K, Machida T, Imamura S, Kawase D, Miyashita K, Fukamachi I, Maeda M, Muraba Y, Koga T, Kobayashi J, Kimura T, Nakajima K, Murakami M.
-
Journal Title
Clin Chim Acta.
Volume: 487
Pages: 54-59
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
[Journal Article] GPIHBP1 autoantibodies in a patient with unexplained chylomicronemia2017
Author(s)
Hu Xuchen、Dallinga-Thie Geesje M.、Hovingh G. Kees、Chang Sandy Y.、Sandoval Norma P.、Dang Tiffany Ly P.、Fukamachi Isamu、Miyashita Kazuya、Nakajima Katsuyuki、Murakami Masami、Fong Loren G.、Ploug Michael、Young Stephen G.、Beigneux Anne P.
-
Journal Title
Journal of Clinical Lipidology
Volume: 11
Issue: 4
Pages: 964-971
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
[Journal Article] Triglyceride content in remnant lipoproteins is significantly increased after food intake and is associated with plasma lipoprotein lipase.2017
Author(s)
Nakajima K, Tokita Y, Sakamaki K, Shimomura Y, Kobayashi J, Kamachi K, Tanaka A, Stanhope KL, Havel PJ, Wang T, Machida T, Murakami M.
-
Journal Title
Clinica Chimica Acta
Volume: 465
Pages: 45-52
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Lipoprotein lipase does not increase significantly in the postprandial plasma.2017
Author(s)
Ishiyama N, Sakamaki K, Shimomura Y, Kotani K, Tsuzaki K, Sakane N, Miyashita K, Fukamachi I, Kobayashi J, Stanhope KL, Havel PJ, Kamachi K, Tanaka A, Tokita Y, Machida T, Murakami M, Nakajima K.
-
Journal Title
Clinica Chimica Acta
Volume: 464
Pages: 204-210
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Presentation] Detection of circulating GPIHBP1-GPIHBP1 autoantibody complex in high TG plasma of patients with a history of acute pancreatitis2019
Author(s)
Katsuyuki Nakajima, Kazuya Miyashita, Isamu Fukamachi, Yoh Umeda, Masumi Ai, Anne Biegneux, Stephen Young, Takumi Nagasawa, Tetsuo Machida, Kiyomi Nakajima, Masami Murakami
Organizer
European Atherosclerosis Society Congress 2019
Related Report
Int'l Joint Research
-
[Presentation] Assessment of training stress by automatically determined Ssalivary cortisol within circadian rhythm in Japanese women long distance runners2019
Author(s)
Kazumi Ushiki, Katsuhiko Tsunekawa, Yoshifumi Shoho, Ryutaro Matsumoto, Yoshimaro Yanagawa, Asuka Nakazawa, Akihiro Yoshida, Osamu Araki, Makoto Nara, Kiyomi Nakajima, Takao Kimura, Masami Murakami
Organizer
The 30th World Congress of World Association of Societies of Pathology and Laboratory Medicine
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
[Book] 臨床検査法提要2020
Author(s)
村上正巳
Total Pages
2012
Publisher
金原出版株式会社
ISBN
9784307050531
Related Report
-
-
-
-
-