Analysis of the function of the anti-angiogenic factor, Tenomodulin, specifically expressed in chordae tendineae cordis

2008 Fiscal Year Final Research Report

• Project/Area Number: 20790997
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: Keio University
• Principal Investigator: KIMURA Naritaka Keio University, 医学部, 助教 (90348657)
• Project Period (FY): 2008 – 2009
• Keywords: 心臓弁膜症 / 血管新生 / 結合組織

Research Abstract

We found that tenomodulin, which is a recently isolated anti-angiogenic factor, was expressed abundantly in the elastin-rich subendothelial outer layer of normal chordae. The immunohistochemical analysis was performed and tenomodulin was locally absent in the ruptured areas of chordae, the same as chordaes of dog after surgically filed. Conditioned medium from cultured chordae interstitial cells strongly inhibited tube formation and mobilization of endothelial cells. These findings provide evidence that tenomodulin is expressed universally in normal chordae in a concentric pattern, and that local absence of tenomodulin is associated with chordae rupture.

Research Products

• [Journal Article] Local Tenomodulin Absence, Angiogenesis, and Matrix Metalloproteinase Activation Are Associated With the Rupture of the Chordae Tendineae Cordis (2008)
  • Author(s): Naritaka Kimura, Chisa Shukunami, Daihiko Hakuno, Masatoyo Yoshioka, Shigenori Miura, Denitsa Docheva, Tokuhiro Kimura, Yasunori Okada, Goki Matsumura, Toshiharu Shin'oka, Ryohei Yozu, Junjiro Kobayashi, Hatsue Ishibashi-Ueda, Yuji Hiraki, Keiichi Fukuda
  • Journal Title: Circulation 118(17) Pages: 1737-1747
  • Peer Reviewed
• [Presentation] 心臓腱索に特異的に発現している血管新生抑制因子Tenomodulinと腱索断裂発症との関連について (2009)
  • Author(s): 木村成卓、伯野大彦、四津良平、福田恵一
  • Organizer: 第19回日本循環薬理学会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-27
• [Presentation] Local Tenomodulin Absence, Angiogenesis, and Matrix Metalloproteinase Activation Are Associated With the Rupture of the Chordae Tendineae Cordis (2009)
  • Author(s): Naritaka Kimura, Chisa Shukunami, Daihiko Hakuno, Masatoyo Yoshioka, Shigenori Miura, Denitsa Docheva, Tokuhiro Kimura, Yasunori Okada, Goki Matsumura, Toshiharu Shin'oka, Ryohei Yozu, Junjiro Kobayashi, Hatsue Ishibashi-Ueda, Yuji Hiraki, Keiichi Fukuda
  • Organizer: 第73回日本循環器学会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Chordae tendineae cordis are covered and protected by the anti-angiogenic factor, Tenomodulin (2008)
  • Author(s): Naritaka Kimura, Daihiko Hakuno, Chisa Shukunami, Yuji Hiraki, Ryohei Yozu, Keiichi Fukuda
  • Organizer: 第25回国際心臓研究学会(ISHR)日本部会
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-06
• [Presentation] The anti-angiogenic factor, Tenomodulin, has a pivotal role in chordae tendineae cordis (2008)
  • Author(s): Naritaka Kimura, Daihiko Hakuno, Chisa Shukunami, Yuji Hiraki, Ryohei Yozu, Keiichi Fukuda
  • Organizer: 第12回日本心不全学会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-17
• [Presentation] Pathological angiogenesis concomitant with the downregulation of tenomodulin and upregulation of VEGF-A causes degeneration and rupture in chordae tendineae cordis (2008)
  • Author(s): Naritaka Kimura, Daihiko Hakuno, Chisa Shukunami, Yuji Hiraki, Ryohei Yozu, Keiichi Fukuda
  • Organizer: American heart association Basic cardiovascular sciences conference 2008
  • Place of Presentation: Keystone
  • Year and Date: 2008-07-29