Elucidation of the onset mechanism of chronic thromboembolic pulmonary hypertension-Creation and analysis of chronic pulmonary thromboembolism

• Project/Area Number: 17K16030
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kurume University
• Principal Investigator: Sugiyama Yoichi 久留米大学, 医学部, 助教 (40750691)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性肺血栓症 / 慢性肺血栓塞栓症 / 内皮障害 / 線溶系異常 / 肺循環 / 慢性血栓塞栓性肺高血圧症 / 慢性血栓塞栓性肺高血圧 / 血管内皮障害 / 循環器内科学

Outline of Final Research Achievements

The purpose of this study is to investigate whether both fibrinolytic and endothelial dysfunction are related to the onset of chronic pulmonary thromboembolism. Although we tried to create a model mouse for chronic pulmonary thromboembolism, it was poorly reproducible. However, pulmonary hypertension remained in the process of creating this model. Therefore, we are focusing on the biological reaction of pulmonary artery endothelial cells to thrombus, and we will elucidate the mechanism of the ability of vascular endothelial cells to phagocytose foreign substances in blood vessels and excrete them out of blood vessels.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は組織プラスミノーゲンアクチベーター(tPA)に関連した線溶系異常と一酸化窒素合成酵素(NOS)障害に関連した内皮障害の双方を有していても、慢性肺血栓塞栓症のモデルマウスを作成することが困難であったことを示したことである。また、異物に対する内皮機能であるAngiophagyの研究を肺血管内皮細胞で試みたことにも学術的意義がある。慢性肺血栓塞栓症のモデルマウスの作成やAngiophagyと慢性肺血栓塞栓症の関連を示すまでに現時点で至らなかったことから、本研究の社会的意義の判断は難しい。

Research Products

• [Journal Article] Clinical hallmarks making diagnosis of infective endocarditis (2019)
  • Author(s): Tahara A, Tahara N, Maeda-Ogata S, Bekki M, Sugiyama Y, Sun J, Honda A, Igata S, FukumotoY
  • Journal Title: J Nucl Cardiol Volume: 印刷中 Issue: 4 Pages: 1391-1393
  • DOI: 10.1007/s12350-019-01686-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Signal intensity of superb micro-vascular imaging associates with the activity of vascular inflammation in Takayasu arteritis. (2019)
  • Author(s): Ito S, Tahara N, Hirakata S, Kaieda S, Tahara A, Maeda-Ogata S, Bekki M, Sugiyama Y, Honda A, Igata S, Kuromatsu R, Nakashima O, Fukumoto Y.
  • Journal Title: J Nucl Cardiol Volume: in press Issue: 3 Pages: 1063-1065
  • DOI: 10.1007/s12350-019-01665-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diagnostic performance of FDG-PET/CTA in native mitral valve endocarditis. (2019)
  • Author(s): Maeda S, Tahara N, Takase F, Bekki M, Tahara A, Honda A, Igata S, Sugiyama Y, Nakamura T, Sun J, Kurata S, Fujimoto K, Abe T, Fukumoto Y.
  • Journal Title: J Nucl Cardiol Volume: 26 Issue: 2 Pages: 681-683
  • DOI: 10.1007/s12350-018-1321-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Utility of the amplitude of RV1+SV5/6 in assessment of pulmonary hypertension. (2018)
  • Author(s): Igata S, Tahara N, Sugiyama Y, Bekki M, Kumanomido J, Tahara A, Honda A, Maeda S, Nashiki K, Nakamura T, Sun J, Abe T, Fukumoto Y.
  • Journal Title: PLoS One. Volume: 13 Issue: 11 Pages: e0206856-e0206856
  • DOI: 10.1371/journal.pone.0206856
  • Peer Reviewed / Open Access
• [Journal Article] Importance of extracardiac FDG uptake to diagnose cardiac sarcoidosis. (2018)
  • Author(s): Tahara N, Bekki M, Sugiyama Y, Tahara A, Fukumoto Y.
  • Journal Title: J Nucl Cardiol. Volume: 印刷中 Issue: 1 Pages: 118-122
  • DOI: 10.1007/s12350-018-1425-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Myocardial metabolic improvement prior to electrocardiographic or volumetric changes of the right ventricle in pulmonary arterial hypertension (2018)
  • Author(s): Nakamura T, Tahara N,Tahara A, Yamagishi SI, Honda A, Igata S, Nitta Y, Bekki M, Nakamura T, Sugiyama Y, Sun J, Takeuchi M, Shimizu M, Yamazaki H, Fukami K, Fukumoto Y
  • Journal Title: J Nucl Cardiol Volume: 25 Issue: 1 Pages: 358-359
  • DOI: 10.1007/s12350-016-0769-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Right ventricular workload assessed by FDG-PET in a patient with residual VSD and infundibular pulmonary stenosis after repair of tetralogy of Fallot (2018)
  • Author(s): Nakamura T, Tahara N, Tahara A, Honda A, Igata S, Bekki M, Sugiyama Y, Sun J, Kumagai E, Kurata S, Fujimoto K, Abe T, Kato S, Tanaka H, Fukumoto Y
  • Journal Title: J Nucl Cardiol Volume: 25 Issue: 3 Pages: 1053-1055
  • DOI: 10.1007/s12350-017-0906-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects (2017)
  • Author(s): Tahara A, Tahara N, Yamagishi SI, Honda A, Igata S, Nitta Y, Bekki M, Nakamura T, Sugiyama Y, Sun J, Takeuchi M, Shimizu M, Yamazaki H, Fukami K, Fukumoto Y
  • Journal Title: Int J Food Sci Nutr Volume: 68 Issue: 8 Pages: 1013-1020
  • DOI: 10.1080/09637486.2017.1318117
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Long Term Survival of Patients with Pulmonary Hypertension at A Single Center (2018)
  • Author(s): 杦山陽一、田原宣広、井形幸代、中村知久、戸次宗久、本多亮博、田原敦子、福本義弘:
  • Organizer: 日本循環器病学会
• [Presentation] 当院で初めて肺動脈血栓内膜除去術を実施した一例, (2018)
  • Author(s): 伊東智樹、杦山陽一、高橋甚彌、大渕綾、仲吉孝晴、大塚昌紀、飛永覚、田原宣広、田中啓之、福本義弘
  • Organizer: 第321回日本内科学会九州地方会
• [Presentation] セレキシパグ導入が困難だった特発性肺動脈性肺高血圧症の一例 (2018)
  • Author(s): 杦山陽一、田原宣広、中村知久、戸次宗久、本多亮博、孫佳慧、田原敦子、井形幸代、熊谷英太、福本義弘:
  • Organizer: 第3回日本肺高血圧症・肺循環学会
• [Presentation] 当院における肺高血圧症の長期予後 (2018)
  • Author(s): 杦山陽一、田原宣広、中村知久、戸次宗久、本多亮博、孫佳慧、田原敦子、井形幸代、熊谷英太、福本義弘:
  • Organizer: 第3回日本肺高血圧症・肺循環学会,
• [Presentation] 当院における肺高血圧症の長期予後, (2018)
  • Author(s): 杦山陽一、田原宣広、中村知久、戸次宗久、本多亮博、孫佳慧、田原敦子、井形幸代、福本義弘:
  • Organizer: 第124回日本循環器病学会九州地方会
• [Presentation] Long-term survival of patients with pulmonary hypertension at a single center. (2018)
  • Author(s): 杦山陽一、田原宣広、戸次宗久、中村知久、本多亮博、孫佳慧、井形幸代、田原敦子、福本義弘
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Myocardial Glucose Metabolism Evaluated by Fasting 18Fluorodeoxyglucose-Positron Emission Tomography in Pulmonary Hypertension (2018)
  • Author(s): Nakamura T, Tahara N, Sugiyama Y, Bekki M, Tahara A, Honda A, Kaida H, Kumagai E, Igata S, Fukumoto Y
  • Organizer: The 6th World Symposium on Pulmonary Hypertension
  • Int'l Joint Research
• [Presentation] Prognostic Findings of Myocardial FDG uptake on PET in Patients with Corticosteroid-naive Cardiac Sarcoidosis (2017)
  • Author(s): Bekki M, Tahara N, Igata S, Tahara A, Nakamura T, Sugiyama Y, Honda A, Fulumoto Y
  • Organizer: The American Heart Association
  • Int'l Joint Research
• [Presentation] Clinical monitoring of inflammatory activity in atherosclerotic disease (2017)
  • Author(s): Tahara N, Tahara A, Honda A, Nitta Y, Igata S, Bekki M, Nakamura T, Sugiyama Y, Sun J, Fulumoto Y
  • Organizer: 第81回日本循環器学会学術集会
  • Invited
• [Presentation] Impact of blood pressure variability and vascular inflammation on endothelial function (2017)
  • Author(s): Akihiro Honda, Nobuhiro Tahara, Atsuko Tahara, Bekki Munehisa, Nakamura Tomohisa, Sugiyama Youichi, Sachiyo Igata, Sho-ichi Yamagishi, Yoshihiro Fukumoto
  • Organizer: 第81回日本循環器学会学術集会
• [Book] イドライン 外来診療 2019』専門医の管理・治療が必要なガイドライン (2019)
  • Author(s): 杦山陽一、田原宣広、福本義弘
  • Publisher: 日経メディカル
• [Book] ガイドライン 外来診療 2018』専門医の管理・治療が必要なガイドライン (2018)
  • Author(s): 杦山陽一、田原宣広、福本義弘
  • Total Pages: 9
  • Publisher: 日経メディカル
• [Book] 核医学・PET.『循環器内科専門医バイブル』 (2018)
  • Author(s): 田原宣広、田原敦子、本多亮博、戸次宗久、杦山陽一、中村知久、孫 佳慧、井形幸代、福本義弘
  • Publisher: 中山書店
• [Book] FDG-PET を用いた動脈硬化の炎症活動性評価 (2017)
  • Author(s): 田原宣広、田原敦子、本多亮博、戸次宗久、中村知久、杦山陽一、孫佳慧、甲斐久史、福本義弘、山岸昌一
  • Total Pages: 10
  • Publisher: 日本臨牀社
• [Book] 慢性肺血栓塞栓症 病因と病態 (2017)
  • Author(s): 田原宣広、田原敦子、本多亮博、戸次宗久、中村知久、杦山陽一、孫佳慧、知花英俊、熊谷英太、福本義弘
  • Total Pages: 7
  • Publisher: 日本臨牀社