Role of neural crest-derived cells in the pathogenesis of pulmonary hypertension and new mechanisms of en endothelin receptor antagonist.

• Project/Area Number: 21790982
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: OHASHI Hiroyuki Mie University, 医学部附属病院, 助教 (70397511)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 肺高血圧 / エンドセリン / 作用機序 / マウス / 低酸素暴露 / 血管病変 / 炎症 / 内皮機能障害 / 神経堤細胞 / 慢性低酸素暴露 / 動物モデル / 幹細胞

Research Abstract

P0-Cre mice, in which P0-Cre positive neural crest-derived cells can be traced in vivo, were exposed to chronic hypobaric hypoxia for 3 weeks. In this model, we could demonstrated the typical findings consistent with pulmonary arterial hypertension, including increased pulmonary artery pressure, right ventricular hypertrophy, and muscularization of small perioheral pulmonary arteries. In this model, we could demonstrated immunohistochemically that some pulmonary vascular cells are neural crest-derived. In this model, we could show that an endothelin receptor antagonist ameliorated pulmonary artery pressure, right ventricular hypertrophy, and muscularization of small pulmonary arteries. We are currently investigating the kinetics of neural crest-derived cells in pulmonary vessels.

Research Products

• [Journal Article] Acute effect of sildenafil on hypoxemic patients (excluding those with Eisenmenger syndrome) with incurable congenital heart disease and disturbed pulmonary vasculature in the mid-term follow-up (2011)
  • Author(s): Mitani Y, Ohashi H, Takabayashi S, Shimpo H, Komada Y.
  • Journal Title: Int J Cardiol. 146(2) Pages: 273-284
  • Peer Reviewed
• [Journal Article] Acute effect of sildenafil on hypoxemic patients (excluding those with Eisenmenger syndrome) with incurable congenital heart disease and disturbed pulmonary vasculature in the mid-term follow-up (2011)
  • Author(s): Mitani Y, Ohashi H, Takabayashi S, Shimpo H, Komada Y.
  • Journal Title: Int J Cardiol Volume: 146(2) Pages: 273-274
  • Peer Reviewed
• [Journal Article] Three-dimentional echocardiographic imaging of a giant eustachian valve in an infant with reversed cyanosis. (2010)
  • Author(s): Yonekawa T, Mitani Y, Ohashi H.
  • Journal Title: Pediatr Cardiol. 31(7) Pages: 1114-1115
  • Peer Reviewed
• [Journal Article] Dynamic right ventricular outflow tract obstruction due to a swinging echolucent cyst on interventricular septum in a 4-year-old girl. (2010)
  • Author(s): Sugino N, Mitani Y, Ohashi H, Hayakawa H, Hosoki K, Takabayashi S, Shimpo H, Komada Y.
  • Journal Title: Circulation 121(12) Pages: 250-251
  • Peer Reviewed
• [Journal Article] Three-dimentional echocardiographic imaging of a giant eustachian valve in an infant with reversed cyanosis. (2010)
  • Author(s): Yonekawa T, Mitani Y, Ohashi H.
  • Journal Title: Pediatr Cardiol Volume: 31(7) Pages: 1114-1115
  • Peer Reviewed
• [Journal Article] In Vivo Plaque Composition and Morphology in Coronary Artery Lesions in The Adolescents and Young Adults Long After Kawasaki Disease: A Virtual (2009)
  • Author(s): Mitani Y, Ohashi H, Sawada H, Ikeyama Y, Hayakawa H, Takabayashi S, Maruyama K, Shimpo H, Komada Y.
  • Journal Title: Histology-Intravascular Ultrasound Study Circulation. 119(21) Pages: 2829-2836
  • Peer Reviewed
• [Journal Article] In Vivo Plaque Composition and Morphology in Coronary Artery Lesions in The Adolescents and Young Adults Long After Kawasaki Disease : A Virtual Histology-Intravascular Ultrasound Study (2009)
  • Author(s): Mitani Y, Ohashi H, Sawada H, Ikeyama Y, Hayakawa H, Takabayashi S, Maruyama K, Shimpo H, Komada Y.
  • Journal Title: Circulation 119(21) Pages: 2829-2836
  • Peer Reviewed
• [Presentation] Impact Of Public-Access Defibrillation At School On The Outcome After Out-Of-Hospital Cardiac Arrest Of Cardiac Origin In Elementary And Middle School Students: A Japanese Nationwide Survey (2010)
  • Author(s): Mitani Y, Ohta K, Ichida F, Nii M, Arakaki Y, Ushinohama H, Ohashi H, Yodoya N, Tateno S, Sato S, Suzuki T, Higaki T, Iwamoto M, Yoshinaga M, Sumitomo N.
  • Organizer: American Heart Association
  • Place of Presentation: Chicago
  • Year and Date: 2010-11-16
• [Presentation] Impact Of Public-Access Defibrillation At School On The Outcome After Out-Of-Hospital Cardiac Arrest Of Cardiac Origin In Elementary And Middle School Students: A Japanese Nationwide Survey (2010)
  • Author(s): Mitani Y, Ohta K, Ichida F, Nii M, Arakaki Y, Ushinohama H, Ohashi H, Yodoya N, Tateno S, Sato S, Suzuki T, Higaki T, Iwamoto M, Yoshinaga M, Sumitomo N.
  • Organizer: American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-16
• [Presentation] Detection of coronary intimal lesions by multi-detector CT in young adults long after Kawasaki disease: Comparison with virtual histology-intravascular ultrasound (2010)
  • Author(s): Ohashi H, Mitani Y
  • Organizer: The 3rd Congress of Asia-Pacific Pediatric Cardiac Society
  • Place of Presentation: Urayasu, Japan
  • Year and Date: 2010-07-07
• [Presentation] New pulmonary vasodilators against intractable pulmonary vascular lesions (excluding Eisenmenger syndrome) associated with congenital heart disease : a mid-term study (2010)
  • Author(s): Mitani Y, Ohashi H, Komada Y
  • Organizer: The 3^<rd> Congress of Asia-Pacific Pediatric Cardiac Society
  • Place of Presentation: Urayasu
  • Year and Date: 2010-07-07
• [Presentation] Detection of coronary intimal lesions by multi-detector CT in young adults long after Kawasaki disease : Comparison with virtual histology-intravascular ultrasound (2010)
  • Author(s): Ohashi H, Mitani Y
  • Organizer: The 3^<rd> Congress of Asia-Pacific Pediatric Cardiac Society
  • Place of Presentation: Urayasu
  • Year and Date: 2010-07-07
• [Presentation] Bosentan promotes incorporation of bone marrow-derived endothelial cells but inhibits infiltration of macrophages into pulmonary vascular lesions in mice exposed to chronic hypoxia: A novel concept of bosentan therapy in pulmonary hypertension (2009)
  • Author(s): Kato T, Sawada H, Maruyama J, Ikeyama Y, Ohashi H, Masuya M, Miyata E, Nakamura S, Shimpo H, Maruyama K, Komada Y, Mitani Y.
  • Organizer: American Heart Association
  • Place of Presentation: Orland
  • Year and Date: 2009-11-17
• [Presentation] In Vivo Plaque Composition and Morphology in Coronary Artery Lesions in The Adolescents and Young Adults Long After Kawasaki Disease: A Virtual Histology-Intravascular Ultrasound Study (2009)
  • Author(s): Mitani M, Ohashi H, Sawada H, Ikeyama Y, Hayakawa H, Komada Y.
  • Organizer: The 5th world congress of pediatric cardiology and cardiac surgery
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2009-06-24
• [Presentation] In Vivo Plaque Composition and Morphology in Coronary Artery Lesions in The Adolescents and Young Adults Long After Kawasaki Disease : A Virtual Histology-Intravascular Ultrasound Study (2009)
  • Author(s): Mitani M, Ohashi H, Sawada H, Ikeyama Y, Hayakawa H, Komada Y.
  • Organizer: The 5^<th> world congress of pediatric cardiology and cardiac surgery
  • Place of Presentation: Cairns (Australia)
  • Year and Date: 2009-06-24