Elucidation of the role of epigenetic regulation by NRSF complex in maintaining cardiac integrity
Project/Area Number |
25860596
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Cardiovascular medicine
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Research Institution | Kyoto University |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 転写因子 / NRSF / 心不全 / エピゲノム / 循環器 / ノックアウトマウス |
Outline of Final Research Achievements |
In this study, I succeeded to generate cardiac-specific NRSF conditional knockout mice (NRSF ccKO) and found that these mice show cardiac dysfunction, malignant arrhythmias and sudden cardiac death, implying that NRSF plays an essential role in maintaining normal cardiac function. To address the underlying mechanisms, I crossed these mice with HDAC1/2 cardiac-specific double heterozygote knockout mice and analyzed NRSF/HDAC1/2 cardiac-specific triple heterozygote knockout mice. I also found that GNAO1 gene expression is increased in NRSF ccKO. To examine the contribution of G alpha O to cardiac dysfunction seen in NRSF ccKO, I treated these mice with PTX and found that PTX improved cardiac function and the survival curve in NRSF ccKO. Currently I am further analyzing the role of G alpha O in the phenotype of NRSF ccKO.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2.2015
Author(s)
Oshita K, Itoh M, Hirashima S, Kuwabara Y, Ishihara K, Kuwahara K, Nakao K, Kimura T, Nakamura K, Ushijima K, Takano M.
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Journal Title
Journal of Molecular and Cellular Cardiology
Volume: 80
Pages: 81-89
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.2014
Author(s)
Yamada Y, Kinoshita H, Kuwahara K, Nakagawa Y, Kuwabara Y, Minami T, Yamada C, Shibata J, Nakao K, Cho K, Arai Y, Yasuno S, Nishikimi T, Ueshima K, Kamakura S, Nishida M, Kiyonaka S, Mori Y, Kimura T, Kangawa K, Nakao K.
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Journal Title
Cardiovasc Research
Volume: 104
Issue: 1
Pages: 183-193
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] The effects of super-flux (high performance) dialyzer on plasma glycosylated pro-B-type natriuretic peptide (proBNP) and glycosylated N-Terminal proBNP in end-stage renal disease patients on dialysis.2014
Author(s)
Nakagawa Y, Nishikimi T, Kuwahara K, Yasuno S, Kinoshita H, Kuwabara Y, Nakao K, Minami T, Yamada C, Ueshima K, Ikeda Y, Okamoto H, Horii K, Nagata K, Kangawa K, Minamino N, Nakao K.
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Journal Title
PLoS One
Volume: 25
Issue: 3
Pages: e92314-e92314
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Angiotensin II type 1a receptor signalling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy2013
Author(s)
Yasuno, S., Kuwahara, K., Kinoshita, H., Yamada, C., Nakagawa, Y., Usami, S., Kuwabara, Y., Ueshima, K., Harada, M., Nishikimi, T., Nakao, K.
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Journal Title
British Journal of Pharmacology
Volume: 170(7)
Issue: 7
Pages: 1384-1395
DOI
Related Report
Peer Reviewed
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[Journal Article] Increased expression of HCN channels in the ventricular myocardium contributes to enhanced arrhythmicity in mouse failing hearts.2013
Author(s)
Kuwabara, Y., Kuwahara, K., Takano, M., Kinoshita, H., Arai, Y., Yasuno, S., Nakagawa, Y., Igata, S., Usami, S., Minami, T., Yamada, Y., Nakao, K., Yamada, C., Shibata, J., Nishikimi, T., Ueshima, K., Nakao, K.
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Journal Title
Journal of the American Heart Association
Volume: 2(3)
Issue: 3
DOI
Related Report
Peer Reviewed
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[Journal Article] Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure2013
Author(s)
Nishikimi, T., Okamoto, H., Nakamura, M., Ogawa, N., Horii, K., Nagata, K., Nakagawa, Y., Kinoshita, H., Yamada, C., Nakao, K., Minami, T., Kuwabara, Y., Kuwahara, K., Masuda, I., Kangawa, K., Minamino, N., Nakao, K.
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Journal Title
PLoS ONE
Volume: 8(1)
Issue: 1
Pages: e53233-e53233
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Increased Expression of HCN channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts2014
Author(s)
Yoshihiro Kuwabara, Koichiro Kuwahara, Makoto Takano, Hideyuki Kinoshita, Yuji Arai, Yasuaki Nakagawa, Shinji Ysuno, Sachiyo Igata, Satoru Usami, Takeya Minami, Yuko Yamada, Kazuhiro Nakao, Chinatsu Yamada, Junko Shibata, Toshio Nishikimi, Kenji Ueshima and Kazuwa Nakao
Organizer
第29回日本不整脈学会・第31回日本心電学会合同学術集会
Place of Presentation
ザ・プリンスパークタワー東京
Year and Date
2014-07-22 – 2014-07-25
Related Report
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