The roll of Kv1.3 and KCa3.1 for the differentiation of effector T cells in patients with heart failure
| Project/Area Number |
15K09129
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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 |
Cardiovascular medicine
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Sato Kayoko 東京女子医科大学, 医学部, 講師 (20246482)
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 敦 東京女子医科大学, 医学部, 助教 (00625626)
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| Research Collaborator |
HAGIWARA nobuhisa
NISHII akiko
KITAMURA kazutaka
SHIGA tsuyoshi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 臨床血管学 / 心不全 / Ｔ細胞 / 免疫記憶 / カリウムチャンネル / サイトカイン / 炎症 / 免疫 / T細胞 |
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| Outline of Final Research Achievements |
Japan becomes the super aging society, and heart failure management becomes the important problem for a prognosis of the cardiovascular disease. In this study, we examined contribution of potassium channels KV1.3 and KCa3.1 which controlled a T cell memory in the heart failure exacerbation.
Expression and a function of KV1.3 which promoted effector memory T cells (TEM) differentiation were enhanced more than that of KCa3.1 which promoted central memory T cells (TCM) differentiation in the patients with severe heart failure. Therefore, the ratios of cytotoxic effector T cells (Teff) Th1 and CD8 CTL T cells increased and increase of inflammatory cytokine IFN γ and Granzyme B was induced, and, as a result, the exacerbation of heart failure might be occurred.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、はじめて心不全の病態増悪に関与するT細胞メモリー機構が明らかとなった。重症心不全では細胞障害性の強いTeffが多く、分化初期段階であるTEM分化に重要なKV1.3の発現と機能亢進が認められた。
カリウムチャンネルは多様なサブファミリーを形成するが、KV1.3は免疫細胞に特異的に機能発現しており、KV1.3阻害剤の開発はTEM抑制効果を有するため、安全性の高い創薬標的と期待される。
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Report
(5 results)
Research Products
(44 results)
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[Journal Article] Statement for Appropriate Clinical Use of PCSK9 Inhibitors2018
Author(s)
Nohara Atsushi、Ohmura Hirotoshi、Okazaki Hiroaki、Ogura Masatsune、Kitagawa Kazuo、Koseki Masahiro、Sato Kayoko、Tsukamoto Kazuhisa、Yamashita Shizuya、On behalf of the Japan Atherosclerosis Society Working Group on Statement for Appropriate Use of PCSK9 Inhibitors
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 25
Issue: 8
Pages: 747-750
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2018-08-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling2018
Author(s)
Tobita T, Nomura S, Fujita T, Morita H, Asano Y, Onoue K, Ito M, Imai Y, Suzuki A, Ko T, Satoh M, Fujita K, Naito AT, Furutani Y, Toko H, Harada M, Amiya E, Hatano M, Takimoto E, Shiga T, Nakanishi T, Sakata Y, Ono M, Saito Y, Takashima S, Hagiwara N, Aburatani H, Komuro I.
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Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 20114-20119
DOI
Related Report
Peer Reviewed / Open Access
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