Yamagishi, Hiroyuki

写真a

Affiliation

School of Medicine, Department of Pediatrics （Shinanomachi）

Position

Professor

External Links
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Academic Background 【 Display / hide 】

  • 1989.04
    -
    1993.03

    Keio University, School of Medicine, 医学研究科内科系小児科学

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, Keio University, Coursework

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Licenses and Qualifications 【 Display / hide 】

  • 日本小児循環器学会　小児循環器専門医

  • 日本人類遺伝学会　臨床遺伝専門医

  • 日本小児科学会　小児科専門医

  • 医師免許

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Research Areas 【 Display / hide 】

  • Life Science / Anatomy

  • Life Science / Medical biochemistry

  • Life Science / Embryonic medicine and pediatrics

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Research Themes 【 Display / hide 】

  • Clinical Cardiac Embryology for Understanding Congenital Heart Diseases, 

    2002.10
    -
    Present

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Papers 【 Display / hide 】

  • Pulmonary arterial hypertension associated with tetralogy of Fallot

    Yasuhara Jun, Yamagishi Hiroyuki

    International heart journal 56   S17 - S21 2015.03

    ISSN  1349-2365

    　View Summary

    <p>Pulmonary arterial hypertension (PAH) is a common postoperative complication in patients with congenital heart disease (CHD). Although the recent clinical classification of pulmonary hypertension divided PAH associated with CHD (PAH–CHD) into several subclasses, the anatomical and hemodynamic features of postoperative PAH–CHD vary enormously. Therefore, it is still difficult to obtain clinical evidence supporting the indication of pulmonary vasodilators for PAH–CHD. We often encounter patients with PAH occurring after surgical treatment of tetralogy of Fallot (TOF), especially patients with major aortopulmonary collateral arteries (MAPCAs). PAH might be caused by pulmonary agenesis, hypoplasia and/or thrombosis, inadequate closure of the ventricular septal defect, relief of the pulmonic stenosis, or an excessively large prior systemic-to-pulmonary shunt. Moreover, patients with TOF and MAPCAs who are diagnosed as inoperable because of the presence of PAH show similar hemodynamic and clinical features to patients with Eisenmenger syndrome. The MAPCAs in these patients usually show hypoplastic and abnormal arborization. Based on our experience, we believe that PAH-targeted therapies are effective in some patients with PAH occurring after surgical treatment of TOF and MAPCAs, especially as an adjunct to percutaneous pulmonary angioplasty. To help classify patients with PAH associated with TOF, especially with MAPCAs, we propose several new subclassifications: “PAH due to hypoplastic pulmonary arterial beds”, “PAH due to abnormal pulmonary arborization”, or “segmental PAH associated with CHD.” A multicenter registry of patients using a unified protocol is essential to explore the indications and efficacy of pulmonary vasodilators for postoperative PAH–CHD.</p>

  • Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart

    Arita Yoh, Nakaoka Yoshikazu, Matsunaga Taichi, Kidoya Hiroyasu, Yamamizu Kohei, Arima Yuichiro, Kataoka-Hashimoto Takahiro, Ikeoka Kuniyasu, Yasui Taku, Masaki Takeshi, Yamamoto Kaori, Higuchi Kaori, Park Jin Sung, Shirai Manabu, Nishiyama Koichi, Yamagishi Hiroyuki, Otsu Kinya, Kurihara Hiroki, Minami Takashi, Yamauchi-Takihara Keiko, Koh Gou Y., Mochizuki Naoki, Takakura Nobuyuki, Sakata Yasushi, Yamashita Jun K., Komuro Issei

    Nature Communications 5 2014.07

    　View Summary

    <p>The origin and developmental mechanisms underlying coronary vessels are not fully elucidated. Here we show that myocardium-derived angiopoietin-1 (Ang1) is essential for coronary vein formation in the developing heart. Cardiomyocyte-specific Ang1 deletion results in defective formation of the subepicardial coronary veins, but had no significant effect on the formation of intramyocardial coronary arteries. The endothelial cells (ECs) of the sinus venosus (SV) are heterogeneous population, composed of APJ-positive and APJ-negative ECs. Among these, the APJ-negative ECs migrate from the SV into the atrial and ventricular myocardium in Ang1-dependent manner. In addition, Ang1 may positively regulate venous differentiation of the subepicardial APJ-negative ECs in the heart. Consistently, in vitro experiments show that Ang1 indeed promotes venous differentiation of the immature ECs. Collectively, our results indicate that myocardial Ang1 positively regulates coronary vein formation presumably by promoting the proliferation, migration and differentiation of immature ECs derived from the SV. © 2014 Macmillan Publishers Limited.</p>

  • MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures

    Muraoka Naoto, Yamakawa Hiroyuki, Miyamoto Kazutaka, Sadahiro Taketaro, Umei Tomohiko, Isomi Mari, Nakashima Hanae, Akiyama Mizuha, Wada Rie, Inagawa Kohei, Nishiyama Takahiko, Kaneda Ruri, Fukuda Toru, Takeda Shu, Tohyama Shugo, Hashimoto Hisayuki, Kawamura Yoshifumi, Goshima Naoki, Aeba Ryo, Yamagishi Hiroyuki, Fukuda Keiichi, Ieda Masaki

    EMBO Journal 33 （ 14 ） 1565 - 1581 2014.07

    ISSN  0261-4189

    　View Summary

    <p>Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors or microRNAs. However, induction of functional cardiomyocytes is inefficient, and molecular mechanisms of direct reprogramming remain undefined. Here, we demonstrate that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated sevenfold more beating iCMs from mouse embryonic fibroblasts and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts. Thus, silencing fibroblast signatures, mediated by miR-133/Snai1, is a key molecular roadblock during cardiac reprogramming.</p>

  • Acute rupture of chordae tendineae of the mitral valve in infants a nationwide survey in Japan exploring a new syndrome

    Shiraishi Isao, Nishimura Kunihiro, Sakaguchi Heima, Abe Tadaaki, Kitano Masataka, Kurosaki Kenichi, Kato Hitoshi, Nakanishi Toshio, Yamagishi Hiroyuki, Sagawa Koichi, Ikeda Yoshihiko, Morisaki Takayuki, Hoashi Takaya, Kagisaki Koji, Ichikawa Hajime

    Circulation 130 （ 13 ） 1053 - 1061 2014

    ISSN  0009-7322

    　View Summary

    <p>Background: Recently, infant cases of acute heart failure attributable to rupture of the mitral chordae tendineae have been reported. However, little is known about the pathogenesis and clinical course of this condition. Methods and Results-Ninety-five children with rupture of mitral chordae tendineae were identified in nationwide surveys of Japan diagnosed from 1995 to 2013. The clinical manifestations, management strategies, and prognosis were investigated. Eighty-one (85%) patients were between 4 and 6 months (median, 5 months) of age. In 63 (66%) patients, rupture occurred during the spring or summer. The underlying conditions before rupture included Kawasaki disease (10 cases), maternally derived anti-SSA antibodies (2 cases), and infective endocarditis (1 case). Surgery was performed in 80 patients (94 operations), and the final operations included plasty of mitral chordae in 52 cases and mechanical valve replacement in 26 cases. The histopathologic examinations of the mitral valves and chordae (n=28) revealed inflammatory reactions with predominant mononuclear cell infiltration in 18 cases (64%) and increased fibrous and myxoid tissue in 11 cases (39%), suggesting that nonbacterial infectious or autoimmune endocarditis and myxoid changes are involved in the pathogenesis. Eight patients (8.4%) died before (n=6) and shortly after (n=2) the operation, and significant neurological complications persisted in 10 cases (11%). Conclusions-Acute heart failure attributable to rupture of the mitral chordae tendineae in infants is a unique disease resulting from diverse causes. This condition should be recognized as a significant cardiovascular disorder that may cause sudden onset of cardiogenic shock and death in infants.</p>

  • Successful lung transplantation in a case with diffuse pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia

    Fukushima H., Mitsuhashi T., Oto T., Sano Y., Kusano K. F., Goto K., Okazaki M., Date H., Kojima Y., Yamagishi H., Takahashi T.

    American Journal of Transplantation 13 （ 12 ） 3278 - 3281 2013.12

    ISSN  1600-6135

    　View Summary

    <p>Diffuse pulmonary arteriovenous malformations (AVMs) are associated with a poor prognosis and the therapeutic strategy remains controversial. We describe a pediatric patient with diffuse pulmonary AVMs associated with hereditary hemorrhagic telangiectasia (HHT), who presented with two cerebral AVMs in the parietal and occipital lobes as well. Of note, successful bilateral lung transplantation not only improved the hypoxemia but also resulted in size reduction of the cerebral AVMs. Although it is essential to consider involvements other than pulmonary AVMs, especially brain AVMs, to decide the indication, lung transplantation can be a viable therapeutic option for patients with diffuse pulmonary AVMs and HHT. The authors describe a successful lung transplant in a patient with diffuse pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia, focusing on its potential to improve cerebral arteriovenous malformations. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.</p>

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Presentations 【 Display / hide 】

  • Molecular mechanisms regulating tissue-specific _expression of Tbx1

    Yamagishi H

    Symposium on Etiology and Morphogenesis of Congenital Cardiovascular Disease in the Post-genomic Era, 

    2002.12
    , 

    Other

  • Tissue-specific regulatory elements of Tbx1, a del.22q11 candidate gene, reveal a molecular cascade involved in pharyngeal arch development

    Yamagishi H, Maeda J, Hu T, McAnally J, Yamagishi C, Srivastava D

    Scientific Sessions of American Heart Association, 

    2002.11
    , 

    Poster presentation

  • Tbx1 is regulated by forkhead proteins through a sonic hedgehog-responsive enhancer

    Maeda J, Yamagishi H, Srivastava D

    Society for Developmental Biology Southwest & Gulf Regional Meeting, 

    2002.09
    , 

    Other

  • Sonic hedgehog is essential for first pharyngeal arch development

    Maeda J, Yamagishi C, Yamagishi H, Srivastava D

    Weinstein Cardiovascular Development Conference, 

    2002.05
    , 

    Poster presentation

  • Tissue-specific regulation of Tbx1 during cardiovascular and pharyngeal arch development

    Yamagishi H, Maeda J, Tonghuan Hu, Yamagishi C, Srivastava D

    Weinstein Cardiovascular Development Conference, 

    2002.05
    , 

    Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • モデル動物とiPS細胞を用いた心臓前駆細胞発生制御による予防医学的基礎研究

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(B), Principal investigator

  • Genetic-environmental interaction for congenital cardiovascular disease

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • T-box遺伝子ファミリー機能解析による先天性心血管疾患発症機構の解明

    2016.04
    -
    2019.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • 動物モデルを用いた先天性心臓流出路異常の予防と新たな治療への基礎的研究（基盤B）

    2013
    -
    2015

    Grant-in-Aid for Scientific Research, Principal investigator

  • 心臓流出路を形成する細胞の発生分化と相互作用を制御する分子機構（基盤B）

    2010
    -
    2012

    Grant-in-Aid for Scientific Research, Principal investigator

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Works 【 Display / hide 】

  • EEP小委員会委員

    2003.10
    -
    2005.09
    , 

    Other

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Awards 【 Display / hide 】

  • 高尾賞

    2012, 日本小児循環器学会, 先天性心疾患の発症分子機構解明と臨床心臓発生学の発展

  • 三四会賞（北里・北島賞）北島賞

    2011, 慶應義塾大学, 心臓血管発生と先天性心疾患発症の分子機構の解明

  • 学会会長賞

    2003.07, 第39回日本小児循環器学会学術集会, 円錐動脈幹の発生における転写因子Tbx1の発現

  • Richard D. Rowe Award in Perinatal Cardiology

    2003.05, Society of Pediatric Research, Tbx1 is regulated by tissue-specific forkhead proteins through a common sonic hedgehog-responsive enhancer

  • 三四会奨励賞

    2003, 慶應義塾大学, 転写因子Tbx1の組織特異的転写制御機構の解明

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Courses Taught 【 Display / hide 】

  • PEDIATRICS: SEMINAR

    2022

  • PEDIATRICS: PRACTICE

    2022

  • PATHOPHYSIOLOGICAL ISSUES IN CHRONIC CARE

    2022

  • LECTURE SERIES, PEDIATRICS

    2022

  • EMBRYOLOGY

    2022

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Courses Previously Taught 【 Display / hide 】

  • 分子細胞生物学（MCBII）中胚葉系臓器の発生III　「心臓・大血管の発生とその異常：臨床心臓発生学のすゝめ」

    Keio University

    2015.04
    -
    2016.03
    , 

    Lecture

  • 循環器内科学「成人の先天性心疾患」

    Keio University

    2015.04
    -
    2016.03
    , 

    Lecture

  • 小児科学「血行動態から学ぶ先天性心疾患の臨床」

    Keio University

    2015.04
    -
    2016.03
    , 

    Lecture

  • 小児科学「発生・形態から学ぶ先天性心疾患の基礎」

    Keio University

    2015.04
    -
    2016.03
    , 

    Lecture

  • 小児科学「小児の症候からのアプローチ：心不全とチアノーゼ」

    Keio University

    2015.04
    -
    2016.03
    , 

    Lecture

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