Elucidation of the role of cardiac fibroblast-derived CNP in myocardial remodeling and its therapeutic significance

• Project/Area Number: 15K19377
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: minami takeya 京都大学, 医学研究科, 客員研究員 (00647208)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 分子心臓病学 / ナトリウム利尿ペプチド

Outline of Final Research Achievements

The purpose of this study is to elucidate the role of C type natriuretic peptide(CNP) secreted from cardiac myofibroblast on cardiac remodeling and the molecular mechanism involved in it by using cardiac constituent cell specific CNP or GC-B knockout mice, and is to clarify the significance of CNP on prevention of cardiac hypertrophy and heart failure. In this study, cardiac hypertrophy due to pressure overload exacerbated in myofibroblast-specific CNP knockout mice compared with control mice. These data suggested that the myofibroblast-derived CNP plays a protective role in pathological myocardial remodeling.

Research Products

• [Journal Article] Endothelium-derived C-type natriuretic peptide contributes to blood pressure regulation by maintaining endothelial integrity. (2017)
  • Author(s): 1. Nakao K, Kuwahara K, Nishikimi T, Nakagawa Y, Kinoshita H, Minami T, Kuwabara Y, Yamada C, Yamada Y, Tokudome T, Nagai-Okatani C, Minamino N, Nakao YM, Yasuno S, Ueshima K, Sone M, Kimura T, Kangawa K, Nakao K.
  • Journal Title: Hypertension Volume: 69 Pages: 289-296
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The renin-angiotensin system promotes arrhythmogenic substrates andalethal arrhythmias in mice with non-ischemic cardiomyopathy (2016)
  • 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
  • Journal Title: Cardiovascular Research Volume: 109 Issue: 1 Pages: 162-173
  • DOI: 10.1093/cvr/cvv248
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • Journal Title: Am J Physiol Regul Integr Comp Physiol. Volume: 309 Issue: 6 Pages: R639-R649
  • DOI: 10.1152/ajpregu.00074.2015
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Adipocyte-derived adrenomedullin suppresses age-and obesity-related increase in blood pressure (2017)
  • Author(s): Kosai Cho, Takeya Minami, Koichiro Kuwahara, Toshio Nishikimi, Hideaki Kinoshita, Kenji Moriuti, Kaoru Koike, Kenji Naoto Minamino, KangawaYasuaki Nakagawa, Hideyuki Kinoshita, Kazuwa Nakao, Takeshi Kimura
  • Organizer: The81st Annual Scientific Meeting of the Japanese Circulation Sciety
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] The mild to moderate stenosis after stenting to Chronic Total Occlusion(CTO) of superficial femoral artery(SFA) could be observed without re-intervention (2016)
  • Author(s): 南丈也,Tay Zar、Wai Phyo、富士榮博昭、小山田尚史、金森徹三、浜中一郎、上田欽造
  • Organizer: 第25回日本心血管インターベンション治療学会学術集会
  • Place of Presentation: 東京
• [Presentation] Stenosis distal to chronic total coronary occlusion (CTO) site improves in chronic phase after recanalization. (2015)
  • Author(s): Takeya Minami, Hiroaki Tabuchi, Nyein Chan Aung,Tatsuya Sugimoto, Hiroaki Fujie, Naofumi Oyamada, Tetsuzo Kanemori, Ichiro Hamanaka, Kinzo Ueda
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Remarks] 京都大学医学部附属病院循環器内科心血管内分泌代謝グループホームページ
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/cat236/