Elucidation of molecular mechanism of stress-induced cardiomyopathy through brain-heart interaction.
Project/Area Number |
25670395
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Cardiovascular medicine
|
Research Institution | Keio University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
ARAI Takahide 慶應義塾大学, 医学部, 講師(非常勤) (00383894)
KANAZAWA Hideaki 慶應義塾大学, 医学部, 特任講師 (40338033)
SUKEGAWA Hiroaki 慶應義塾大学, 医学部, 助教 (60535607)
TABEI Ryota 慶應義塾大学, 医学部, 助教 (20573322)
MUNAKATA Masahito 慶應義塾大学, 医学部, 共同研究員 (40445284)
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
|
Keywords | ストレス / 脳 / サイトカイン / 脳心連関 / 炎症 / 臓器連関 |
Outline of Final Research Achievements |
Major emotional stress may induce stress cardiomyopathy (SC), although the precise molecular mechanisms remain unclear. Using an animal model of SC, we first located the central cardiac sympathetic nerves (CSNs) in the hypothalamus innervating the left ventricular (LV) apex, and then investigated the gene expression changes in these regions. We found that chemokine ligand 2 (Ccl2), produced by activated astrocytes, strongly stimulated the central CSNs. The subsequent sympathetic activation upregulated neuropeptide Y (NPY) expression in both the stellate ganglion (SG) and CSNs. NPY in turn had a negative inotropic effect and strongly blocked -adrenergic stimulation. Thus, administration of Ccl2 into the central neurons evoked SC and increased NPY at the SG. Moreover, siRNA downregulation of NPY in the SG completely abrogated the induced SC. Overall, our results provide to explain how emotional stress affects molecular signals in the brain, leading to LV apical ballooning.
|
Report
(3 results)
Research Products
(13 results)
-
[Journal Article] A massive floating culture system with metabolic purification for human induced pluripotent stem cell-derived cardiomyocytes.2014
Author(s)
Natsuko Hemmi, Shugo Tohyama, Kazuaki Nakajima, Hideaki Kanazawa, Tomohisa Seki, Yoshikazu Kishino, Akinori Hirano, Marina Okada, Ryota Tabei, Rei Ohno, Chihana Fujita, Fumiyuki Hattori, Shinsuke Yuasa, Motoaki Sano, Jun Fujita, and Keiichi Fukuda.
-
Journal Title
Stem Cells Translational Medicine.
Volume: 3
Pages: 1473-1483
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] Derivation of Transgene-free Human Induced Pluripotent Stem Cells from Human Peripheral T Cells in Defined Culture Conditions.2014
Author(s)
Yoshikazu Kishino, Tomohisa Seki, Jun Fujita, Shinsuke Yuasa, Shugo Tohyama, Akira Kunitomi, Ryota Tabei, Kazuaki Nakajima, Marina Okada, Akinori Hirano, Hideaki Kanazawa, Keiichi Fukuda.
-
Journal Title
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] Distinct Metabolic Flow Enables Large-Scale Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes.2013
Author(s)
Tohyama S, Hattori F, Sano M, Hishiki T, Nagahata Y, Matsuura T, Hashimoto H, Suzuki T, Yamashita H, Satoh Y, Egashira T, Seki T, Muraoka N, Yamakawa H, Ohgino Y, Tanaka T, Yoichi M, Yuasa S, Murata M, Suematsu M, Fukuda K.
-
Journal Title
Cell Stem Cell
Volume: 12
Pages: 127-137
Related Report
Peer Reviewed
-
[Journal Article] Disparity in the application of guideline-based medical therapy after percutaneous coronary intervention: analysis from the Japanese prospective multicenter registry.2013
Author(s)
Endo A, Kohsaka S, Miyata H, Kawamura A, Noma S, Suzuki M, Koyama T, Ishikawa S, Momiyama Y, Nakagawa S, Sueyoshi K, Takagi S, Takahashi T, Sato Y, Ogawa S, Fukuda K.
-
Journal Title
Am J Cardiovasc Drugs.
Volume: 13
Pages: 103-12
Related Report
Peer Reviewed
-
[Journal Article] Diagnostic value of portable electrocardiogram (Cardiophone) in patients complaining of palpitation.2013
Author(s)
Aizawa Y, Takatsuki S, Suenaga Y, Kimura T, Nishiyama N, Fukumoto K, Tanimoto Y, Tanimoto K, Kohsaka S, Fukuda Y, Murata M, Miyoshi S, Sato T, Iwanaga S, Ogawa S, Fukuda K.
-
Journal Title
Int J Cardiol.
Volume: 168(3)
Pages: 2925-7
Related Report
Peer Reviewed
-
[Journal Article] Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction.2013
Author(s)
Yan X, Anzai A, Katsumata Y, Matsuhashi T, Ito K, Endo J, Yamamoto T, Takeshima A, Shinmura K, Shen W, Fukuda K, Sano M.
-
Journal Title
J Mol Cell Cardiol.
Volume: 62
Pages: 24-35
Related Report
Peer Reviewed
-
-
[Presentation] 心臓交感神経から心臓病を診る2014
Author(s)
金澤英明、木村謙介、荒井隆秀、福田恵一
Organizer
第35回日本循環制御医学会総会
Place of Presentation
九州大学医学部百年講堂
Year and Date
2014-07-04 – 2014-07-05
Related Report
Invited
-
-
-
-
[Book] 循環制御2014
Author(s)
金澤英明、木村謙介、荒井隆秀、福田恵一
Publisher
小玉株式会社出版部
Related Report
-