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

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: Cardiovascular Research Volume: 104 Pages: 183-193
  • DOI: 10.1093/cvr/cvu185
  • NAID: 120005619790
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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
  • DOI: 10.1371/journal.pone.0092314
  • NAID: 120006651999
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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
• [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