Elucidation of novel mechanism in cardiac fibrosis

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590815
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kinki University
• Principal Investigator: IWANAGA Yoshitaka 近畿大学, 医学部, 准教授 (80360816)
• Co-Investigator(Renkei-kenkyūsha): ONO Koh 京都大学, 医学研究科, 講師 (00359275) ; KOSHIMIZU Taka-aki 自治医科大学, 医学部, 准教授 (20392491)
• Project Period (FY): 2010 – 2012
• Keywords: 分子心臓病態学

Research Abstract

We elucidated two novel mechanism in cardiac fibrosis. First, we have shown that metastasis-associated protein, S100A4 mediates pathological cardiac fibrosis through the modulation of p53 in cardiac fibroblast. Second, we have shown that the activation of vasopressin type 1a receptor contributes to the profibrotic effect of angiotensin II in the heart as well as the fibrosis and onset of heart failure seen in pressure-overloaded LV for the first time. In the future, we will investigate whether the modulation of these two factors may offer therapeutic benefits in heart failure.

Research Products

• [Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts (2013)
  • Author(s): Yodo Tamaki, Yoshitaka Iwanaga (Corresponding Author), Shinichiro Niizuma, Tsuneaki Kawashima, Takao Kato, Yasutaka Inuzuka, Takahiro Horie, Hanako Morooka, Toru Takase, Yasumitsu Akahashi, Kazuhiro Kobuke, Koh Ono, Tetsuo Shioi, Soren P Sheikh, Noona Ambartsumian, Eugene Lukanidin, Taka-aki Koshimizu, Shunichi Miyazaki, Takeshi Kimura
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 72-81
• [Journal Article] Chronic Administration of Oral Vasopressin Type 2 Receptor Antagonist, Tolvaptan Exerts Both Myocardial and Renal Protective Effects in Rats with Hypertensive Heart Failure (2012)
  • Author(s): Hanako Morooka, Yoshitaka Iwanaga (Corresponding Author), Yodo Tamaki, Toru Takase, Yasumitsu Akahoshi, Yasumasa Nakano, Hiroyuki Fujiki, Shunichi Miyazaki
  • Journal Title: Circ Heart Fail Volume: 5 Pages: 484-492
• [Presentation] Does vasopressin type1a receptor antagonist exert beneficial effects or additive effects to type2 receptor antagonist, tolvaptan in heart failure animals? (2013)
  • Author(s): Tomoyuki Ikeda, Yoshitaka Iwanaga
  • Organizer: 第75回日本循環器学会総会
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20130000
• [Presentation] Interaction of S100A4 with p53 in fibroblasts modulates cardiac fibrosis through two distinct mechanisms (2012)
  • Author(s): Yodo Tamaki, Yoshitaka Iwanaga
  • Organizer: ESC Congress 2012, Munich
  • Place of Presentation: Germany
  • Year and Date: 20120000
• [Presentation] Chronic administration of oral vasopressin type 2 receptor blocker, tolvaptan exerts both myocardial and renal protective effects in rats with hypertensive heart failure (2011)
  • Author(s): Hanako Morooka, Yoshitaka Iwanaga
  • Organizer: 85th AHA (American Heart Association) Scientific Sessions
  • Place of Presentation: Orland, USA
  • Year and Date: 20110000
• [Presentation] Vasopressin type 1a receptor deficiency prevents the onset of heart failure: possible link with myocardial fibrosis (2010)
  • Author(s): Toru Takase, Yoshitaka Iwanaga
  • Organizer: 84th AHA (American Heart Association) Scientific Sessions
  • Place of Presentation: Chicago, USA
  • Year and Date: 20100000