Significance of adrenomedullin in cardiac remodeling through the regulation of lymphangiogenesis and inflammation

• Project/Area Number: 25860597
• 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(系)研究科(研究院), 研究員 (00647208)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥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: 循環器 / 遺伝子 / 液性因子 / リモデリング / ノックアウトマウス / 生理活性 / 炎症 / 心筋リモデリング

Outline of Final Research Achievements

In this study, we examined the role of adrenomedullin (ADM) in pathological cardiac remodeling. We succeeded to create cardiac-specific ADM conditional knock out mice (ADM ccKO) and found that their cardiac structure and function did not significantly differ from control mice in both basal- and pressure overloaded-conditions. We also created cardiac fibroblast ADM knockout mice (ADM fcKO), whose cardiac function and structure were not significantly different from those of control mice. These results suggest that ADM produced by other cells than either cardiac myocytes or cardiac fibroblasts can compensate for the loss of ADM in cardiac myocytes or fibroblasts, respectively.

Research Products

• [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.
  • Journal Title: Cardiovasc Research Volume: 104 Issue: 1 Pages: 183-193
  • DOI: 10.1093/cvr/cvu185
  • NAID: 120005619790
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: PLoS One Volume: 25 Issue: 3 Pages: e92314-e92314
  • DOI: 10.1371/journal.pone.0092314
  • NAID: 120007100132
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Journal of the American Heart Association Volume: 2(3) Issue: 3
  • DOI: 10.1161/jaha.113.000150
  • Peer Reviewed
• [Journal Article] Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure (2013)
  • 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.
  • Journal Title: PLoS ONE Volume: 8(1) Issue: 1 Pages: e53233-e53233
  • DOI: 10.1371/journal.pone.0053233
  • NAID: 120005241437
  • Peer Reviewed
• [Presentation] Increased Expression of HCN channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts (2014)
  • 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
• [Presentation] Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodeling in mice (2014)
  • Author(s): Minami T, Kuwahara K, Kuwabara Y, Cho K, Kinoshita H, Nakagawa Y, Ueda K, Kimura T
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: 京都
  • Year and Date: 2014-04-14 – 2014-04-18
• [Presentation] 血管壁ナトリウム利尿ペプチド系の意義の解明－血管内皮細胞特異的C型ナトリウム利尿ペプチド(CNP)ノックアウトマウスの解析－ (2013)
  • Author(s): 中尾一泰 桑原宏一郎 錦見俊雄 中川靖章 木下秀之 宇佐美覚 桑原佳宏 南丈也 山田千夏 山田優子 保野慎治 上嶋健治 曽根正勝 寒川賢治 中尾一和
  • Organizer: 第50回 臨床分子医学会
  • Place of Presentation: 東京
  • Year and Date: 2013-04-12
• [Remarks] 京都大学循環器内科ホームページ
  • URL: http://kyoto-u-cardio.jp/
• [Remarks] 研究室ホームページ
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html
• [Remarks] 京都大学大学院医学研究科内分泌代謝内科学 心臓グループ
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html