The effects of left ventricular unloading on cardiomyocyte regeneration

• Project/Area Number: 26461128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nagoya University
• Principal Investigator: UNNO Kazumasa 名古屋大学, 医学部附属病院, 助教 (40709119)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 心筋細胞 / 細胞分裂 / 多倍体細胞 / 心筋細胞分裂 / 核内受容体 / エピゲノム修飾 / 単核心筋細胞 / 核酸合成 / 内因性心筋再生 / 心筋再生

Outline of Final Research Achievements

Over the last decade, increasing evidence has suggested that the adult mammalian heart exhibits regenerative capacity due to proliferation of existing cardiomyocytes. It is unclear, however, if external stress may reactivate or upregulate the endogenous cardiac regenerative capacity. Acute left ventricle pressure overload was produced by constriction of ascending aorta (AAC) in adult mouse hearts. One week following AAC, ventricular afterload was normalized in a subset of animal through removal of the aortic constriction (de-AAC). Interestingly, acute decrease in ventricular overload with de-AAC was marked by an increase in cardiomyocyte proliferation. Those cardiomyocytes positive for thymidine analog labeling were characteristic of newly generated cardiomyocytes, with smaller size and single diploid nuclei. Moreover, newly generated cardiomyocytes were found to reside in close proximity to one another, consistent with regional stimulation of cellular proliferation.

Research Products

• [Journal Article] Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction. (2017)
  • Author(s): Tsuda T, Takefuji M, Wettschureck N, Kotani K, Morimoto R, Okumura T, Kaur H, Eguchi S, Sakaguchi T, Ishihama S, Kikuchi R, Unno K, Matsushita K, Ishikawa S, Offermanns S, Murohara T.
  • Journal Title: J Exp Med. Volume: 214 Issue: 7 Pages: 1877-1877
  • DOI: 10.1084/jem.20161924
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diallyl Trisulfide Augments Ischemia-Induced Angiogenesis via an Endothelial Nitric Oxide Synthase-Dependent Mechanism (2017)
  • Author(s): Hayashida R, Kondo K, Morita S, Unno K, Shintani S, Shimizu Y, Calvert JW, Shibata R, Murohara T.
  • Journal Title: Circulation Journal Volume: 81 Issue: 6 Pages: 870-878
  • DOI: 10.1253/circj.CJ-16-1097
  • NAID: 130005679693
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A Transient Up-regulation of Aldh1a2/RARs /Wif-1 Axis Induces Cell-cycle Arrest in Neonatal Heart (2018)
  • Author(s): Fujikawa Y, Unno K, Murohara T
  • Organizer: BCBR
  • Int'l Joint Research
• [Presentation] A Transient Up-regulation of Retinoic Acid Signaling Induces Cell-Cycle Arrest in Neonatal Mammalian Heart (2017)
  • Author(s): Yusuke Fujikawa, Kazumasa Unno, Shingo Narita, Ryo Hayashida, Kazuhisa Kondo, Mikito Takefuji, Toyoaki Murohara.
  • Organizer: AHA Annual Meeting
  • Int'l Joint Research
• [Book] 循環器内科学 (2014)
  • Author(s): 海野一雅、室原豊明、以下省略
  • Total Pages: 516
  • Publisher: 科学評論社