Novel therapuetic and diagnostic approaches for monosodium urate crystal induced coronary vascular inflammation
Project/Area Number |
19K17511
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 尿酸 / 炎症 / 結晶 / OCT / 痛風 / 高尿酸血症 / インターロイキン / 冠動脈 / 尿酸塩結晶 / 偏光 / 好中球 / 光干渉断層装置 / NETs / ブタ / 光干渉断層 / IL-1β / 虚血性心疾患 |
Outline of Research at the Start |
血清尿酸値の上昇は心血管病の予後マーカーであるが、尿酸低下療法が心血管疾患を抑制したとするエビデンスは少ない。尿酸は結晶として析出することで局所のIL-1β産生を介して好中球を誘導し慢性炎症を形成する。このことは小動物を用いた基礎的検討で明らかとされているが、適切な画像診断法がなく、痛風患者で冠動脈に尿酸塩結晶が蓄積しプラークの形成に寄与しているかは明らかでない。本研究は、尿酸塩結晶のもつ複屈折性に注目し厚み1μmの尿酸塩さえ描出できるPS-μOCT診断法を開発することで、冠動脈に対する尿酸の直接的関わりを検討し同時に動物モデルを作成し痛風患者の治療法として抗炎症療法の開発を目指すものである。
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Outline of Final Research Achievements |
Coronary crystalline components induce macrophage chemotaxis, helping them secreting inflammatory cytokines via inflammasome activation. Cross-polarized micro optical coherence tomography (CP-uOCT) is a novel diagnostic approach to pursue birefringent crystals, such as monosodium urate crystals (MSU), in situ. MSU is known to induce local inflammation at a site of gouty tophus. Aims of this study were 1) to develop a novel pig model with highly MSU depositions to his/her coronary arteries, and 2) to attest catheter-based CP-uOCT imaging in the model in vivo. Although we were successful to develop the pig model at acute phase, it was difficult to keep the pigs due to severe vascular injury made to the coronary artery. We then developed another animal model of atherosclerosis. Rabbits were fed with high-fat diet to receive balloon injury to their iliac arteries. The models exhibited cholesterol crystal depositions. The crystal deposition was increased over time from 1 month to 3 months.
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Academic Significance and Societal Importance of the Research Achievements |
尿酸やコレステロール結晶による血管炎症を実臨床、ヒト生体内で画像化する技術を確立することで、従来の概念とは異なるハイリスクの虚血性心疾患患者を抽出することが期待できる。また、好中球NETs/NETosiがマクロファージを主体とする結晶性炎症に支持的に作用することが動物実験レベルで証明できれば、これらに阻害的に作用する薬剤の開発につなげることができ、将来的に結晶性炎症を標的とした新しい抗動脈硬化治療戦略に帰結させることができる。
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Report
(5 results)
Research Products
(38 results)
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[Journal Article] Prediction of the development of delirium after transcatheter aortic valve implantation using preoperative brain perfusion SPECT2022
Author(s)
Takeuchi Masashi, Suzuki Hideaki, Matsumoto Yasuharu, Kikuchi Yoku, Takanami Kentaro, Wagatsuma Toshihiro, Sugisawa Jun, Tsuchiya Satoshi, Nishimiya Kensuke, Hao Kiyotaka, Godo Shigeo, Shindo Tomohiko, Shiroto Takashi, Takahashi Jun, Kumagai Kiichiro, Kohzuki Masahiro, et al.
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Journal Title
PLOS ONE
Volume: 17
Issue: 11
Pages: e0276447-e0276447
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Fractal analysis of dynamic stress CT-perfusion imaging for detection of hemodynamically relevant coronary artery disease2022
Author(s)
Michallek F, Nakamura S, Kurita T, Ota H, Nishimiya K, Ogawa R, Shizuka T, Nakashima H, Wang YN, Ito T, Sakuma H, Dewey M, Kitagawa K
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Journal Title
J Am Coll Cardiol Img
Volume: In-press
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo.2021
Author(s)
Watanabe T, Matsumoto Y, Nishimiya K, Shindo T, Amamizu H, Sugisawa J, Tsuchiya S, Sato K, Morosawa S, Ohyama K, Watanabe-Asaka T, Hayashi M, Kawai Y, Takahashi J, Yasuda S, Shimokawa H.
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Journal Title
PLoS One.
Volume: 16
Issue: 9
Pages: e0257175-e0257175
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Beneficial effects of exercise training on physical performance in patients with vasospastic angina2021
Author(s)
Sugisawa Jun,Matsumoto Yasuharu,Takeuchi Masashi,Suda Akira,Tsuchiya Satoshi,Ohyama Kazuma,Nishimiya Kensuke,Akizuki Mina,Sato Koichi,Ohura Shoko,Ota Hideki,Ikeda Shohei,Shindo Tomohiko,Kikuchi Yoku,Hao Kiyotaka,Shiroto Takashi,Takahashi Jun,Miyata Satoshi,Sakata Yasuhiko,Takase Kei,Kohzuki Masahiro,Shimokawa Hiroaki
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Journal Title
International Journal of Cardiology
Volume: 328
Pages: 14-21
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Association between Coronary Atherosclerotic and Inflammatory Changes and Magnitude of Myocardial Bridge2022
Author(s)
Tasuku Watanabe, Kensuke Nishimiya, Hideaki Ota, Satoshi Higuchi, Erika Yamamoto, Satoshi Takeuchi, Kento Fukui, Akira Suda, Shigeo Godo, Tomohiko Shindo, Kiyotaka Hao, Yoku Kikuchi, Jun Takahashi and Satoshi Yasuda
Organizer
第86回日本循環器学会総会
Related Report
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[Presentation] Coronary Atherosclerotic and Inflammatory Changes for Varying Lengths of Myocardial Bridge2021
Author(s)
Tasuku Watanabe, Kensuke Nishimiya, Hideaki Ota, Satoshi Higuchi, Erika Yamamoto, Satoshi Takeuchi, Kento Fukui, Akira Suda, Shigeo Godo, Tomohiko Shindo, Kiyotaka Hao, Yoku Kikuchi, Jun Takahashi and Satoshi Yasuda
Organizer
AHA scientific session 2021
Related Report
Int'l Joint Research
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[Presentation] Clinical implications of coronary artery morphology of patients with ischemia and non-obstructive coronary artery disease (INOCA) -An intracoronary OCT study-2020
Author(s)
Kensuke Nishimiya, MD, PhD; Akira Suda, MD, PhD; Kiyotaka Hao, MD, PhD; Jun Takahashi, MD, PhD; Yasuharu Matsumoto, MD, PhD; Koichi Satoh, MD, PhD; Jun Sugisawa, MD, PhD; Tomohiko Shindo, MD, PhD; Shigeo Godo, MD, PhD; Yoku Kikuchi, MD, PhD; Takashi Shiroto, MD, PhD; Hiroaki Shimokawa, MD, PhD.
Organizer
European Society of Cardiology
Related Report
Invited
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[Presentation] Exercise Training Ameliorates Vasodilator Capacity of Coronary Microvessels in Patients with Vasospastic Angina A New Therapeutic Approach for the Coronary Functional Disorder.2019
Author(s)
Sugisawa J, Matsumoto Y, Suda A, Tsuchiya S, Ohyama K, Takeuchi M, Nishimiya K, Akizuki M, Sato K, Kajitani S, Ota H, Ikeda S, Shindo T, Kikuchi Y, Hao K, Shiroto T, Takahashi J, Miyata S, Sakata Y, Takase K, Kohzuki M, Shimokawa H.
Organizer
American Heart Association Scientific Session 2019
Related Report
Int'l Joint Research
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[Presentation] Low-intensity pulsed ultrasound ameliorates DES-induced coronary adventitial inflammation and hyperconstricting responses in pigs in vivo -A novel non-invasive therapy for coronary inflammation2019
Author(s)
Watanabe T, Matsumoto Y, Amamizu H, Morosawa S, Ohyama K, Nishimiya K, Shindo T, Suda A, Ikeda S, Kikuchi Y, Hao K, Shiroto T, Takahashi J, Shimokawa H.
Organizer
European Society of Cardiology 2019
Related Report
Int'l Joint Research
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