Elucidation of significance of vascular CNP-GC-B system in vascular integrity and pathology
Project/Area Number |
26670400
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Cardiovascular medicine
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Research Institution | Kyoto University |
Principal Investigator |
Kuwahara Koichiro 京都大学, 医学(系)研究科(研究院), 講師 (30402887)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | ナトリウム利尿ペプチド / 血管内皮 / 血圧 / 循環器 |
Outline of Final Research Achievements |
In this study, we studied the role of vascular CNP-GC-B system in vascular homeostasis. We generated vascular endothelial cell-specific CNP knockout (CNP ecKO) mice and measured blood pressures in these CNP ecKO mice. CNP ecKO mice showed significantly higher blood pressure than control mice. In CNP ecKO, endothelium-dependent vasorelaxation was impaired and endothelial expression of vasoconstrictive endothelin-1 was increased. By contrast, vascular smooth muscle cell-specific GC-B knockout (GC-B smcKO) mice exhibited blood pressures similar to control mice, and acetylcholine-induced vasorelaxation was preserved. These results demonstrate that endothelium-derived CNP contributes to the chronic regulation of vascular tone and systemic blood pressure by maintaining endothelial function independently of vascular smooth muscle GC-B.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] The renin-angiotensin system promotes arrhythmogenic substrates andalethal arrhythmias in mice with non-ischemic cardiomyopathy2016
Author(s)
Yamada C, Kuwahara K, Yamazaki M, Nakagawa Y, Nishikimi T, Kinoshita H, Kuwabara Y, Minami T, Yamada Y, Shibata J, Nakao K, , Arai Y, Honjo H, Kamiya K, Nakao K, Kimura T
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Journal Title
Cardiovascular Research
Volume: 109
Issue: 1
Pages: 162-173
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pro-B-type natriuretic peptide is cleaved intracellularly: impact of distance between O-glycosylation and cleavage sites.2015
Author(s)
Nishikimi T, Nakagawa Y, Minamino N, Ikeda M, Tabei K, Fujishima A, Takayama K, Akimoto K, Yamada C, Nakao K, Minami T, Kuwabara Y, Kinoshita H, Tsutamoto T, Ishimitsu T, Kangawa K, Kuwahara K, Nakao K
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Journal Title
Am J Physiol Regul Integr Comp Physiol.
Volume: 309
Issue: 6
Pages: R639-R649
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The local CNP/GC-B system in the growth plate is responsible for physiological endochondral bone growth.2015
Author(s)
Nakao, K., Osawa, K., Yasoda, A., Yamanaka, S., Fujii, T., Kondo, E., Koyama, N., Kanamoto, N., Miura, M., Kuwahara, K., Akiyama, H., Bessho, K., and Nakao, K..
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Journal Title
Scientific Reports
Volume: 5
Issue: 1
Pages: 1-11
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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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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[Presentation] Role of O-glycosylation in N-terminal region of human proBNP in its processing mechanisms2014
Author(s)
Yasuaki Nakagawa, Toshio Nishikimi, Koichiro Kuwahara, Shinji Yasuno, Hideyuki Kinoshita, Yoshihiro Kuwabara, Kazuhiro Nakao, Chinatsu Yamada, Kenji Ueshima, Naoto Minamino, Takeshi Kimura, Kazuwa Nakao
Organizer
AHA Scientific Sessoins 2014
Place of Presentation
Chicago
Year and Date
2014-11-15 – 2014-11-19
Related Report
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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, Kazuwa Nakao
Organizer
第31回日本心電学会学術集会,
Place of Presentation
東京
Year and Date
2014-07-22 – 2014-07-25
Related Report
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