New approach in rodent model using high-frequency ultrasound imaging systems and development of novel therapies for fetal heart failure
Project/Area Number |
17K16316
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Embryonic/Neonatal medicine
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Research Institution | National Center for Child Health and Development (2019) Mie University (2017-2018) |
Principal Investigator |
Miyoshi Takekazu 国立研究開発法人国立成育医療研究センター, 臨床研究センター, 上級専門職 (70626697)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 胎児心不全 / 胎児心疾患 / 胎児治療 / 小動物用超音波高解像度イメージングシステム / PDE5阻害剤 / マウス / 小動物用超音波高解像度イメージング / 先天性心疾患 / 胎児・新生児医学 / 先天異常学 / 遺伝子改変マウス |
Outline of Final Research Achievements |
We first used an ultra-high-frequency ultrasound imaging systemin utero and demonstrated that Hey2 knockout embryos had worsening right ventricular hypoplasia and marked left ventricular (LV) dilatation as gestation progressed. In both ventricles, fractional shortening was significantly lower in Hey2 knockout embryos than in wild-type embryos, indicating that the embryos can be used as a murine model of fetal heart failure. Subsequently, we evaluated the effect of tadalafil treatment (0.04 or 0.08 mg/ml; T0.04 or T0.08 groups, respectively) on fetoplacental circulation in Hey2 knockout embryos. LV fractional shortening was significantly higher in the T0.04 group than in control, whereas LV dilation, mitral E/A ratio, and umbilical artery resistance index were not significantly different among all groups. Therefore, our findings suggest that tadalafil is a potential agent to treat impaired fetal ventricular systolic function.
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Academic Significance and Societal Importance of the Research Achievements |
小動物用超音波高解像度イメージングシステムを応用し、従来困難であったマウス胎仔心臓の機能的評価をリアルタイムに行なうことで、Hey2ホモ接合型欠損マウスが胎児心不全モデルマウスになりうることを初めて示した。本実験系は、様々な遺伝子改変マウスの胎仔心機能や循環動態の観察などに広く応用できると考えられる。 さらに、本実験系を用いて、PDE5阻害剤が胎児心不全に対する新規治療法となりうることを初めて示した。胎仔心臓に対するPDE5阻害剤の作用機序や最適な投与量については更なる検討が必要であるが、胎児水腫への進行を抑制し、在胎期間を延長させることで、胎児心疾患の予後改善に寄与すると考えている。
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Plasma natriuretic peptide levels reflect the status of the heart failure in fetuses with arrhythmia.2020
Author(s)
Miyoshi T, Hosoda H, Kurosaki K, Shiraishi I, Nakai M, Nishimura K, Miyazato M, Kangawa K, Ikeda T, Yoshimatsu J, Minamino N.
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Journal Title
The Journal of Maternal-Fetal & Neonatal Medicine
Volume: -
Issue: 12
Pages: 1883-1889
DOI
Related Report
Peer Reviewed
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[Journal Article] Antenatal Therapy for Fetal Supraventricular Tachyarrhythmias2019
Author(s)
Miyoshi T, Maeno Y, Hamasaki T, Inamura N, Yasukochi S, Kawataki M, Horigome H, Yoda H, Taketazu M, Nii M, Hagiwara A, Kato H, Shimizu W, Shiraishi I, Sakaguchi H, Ueda K, Katsuragi S, Yamamoto H, Sago H, Ikeda T
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Journal Title
Journal of the American College of Cardiology
Volume: 74
Issue: 7
Pages: 874-885
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Predicting postpartum cardiac events in pregnant women with complete atrioventricular block.2019
Author(s)
Nakashima A, Miyoshi T, Kamiya CA, Nishio M, Horiuchi C, Tsuritani M, Iwanaga N, Katsuragi S, Neki R, Ikeda T, Yoshimatsu J.
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Journal Title
Journal of Cardiology
Volume: 74
Issue: 4
Pages: 347-352
DOI
Related Report
Peer Reviewed
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[Journal Article] Maternal and fetal outcomes in pregnancy complicated with Eisenmenger syndrome.2019
Author(s)
Katsurahgi S, Kamiya C, Yamanaka K, Neki R, Miyoshi T, Iwanaga N, Horiuchi C, Tanaka H, Yoshimatsu J, Niwa K, Takagi Y, Ogo T, Nakanishi N, Ikeda T.
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Journal Title
Taiwanese Journal of Obstetrics & Gynecology
Volume: 58
Issue: 2
Pages: 183-187
DOI
Related Report
Peer Reviewed
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[Journal Article] Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study2019
Author(s)
Takekazu Miyoshi, Hisato Oku, Saiko Asahara, Akira Okamoto, Koichi Kokame, Michikazu Nakai, Kunihiro Nishimura, Fumiyuki Otsuka, Aya Higashiyama, Jun Yoshimatsu, Toshiyuki Miyata
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Journal Title
International Journal of Hematology
Volume: 印刷中
Issue: 6
Pages: 641-649
DOI
Related Report
Peer Reviewed
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[Journal Article] Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions.2019
Author(s)
Tachibana Ryota, Umekawa Takashi, Yoshikawa Kento, Owa Takao, Magawa Shoichi, Furuhashi Fumi, Tsuji Makoto, Maki Shintaro, Shimada Kyoko, Kaneda K. Michiko, Nii Masafumi, Tanaka Hiroaki, Tanaka Kayo, Kamimoto Yuki, Kondo Eiji, Kato Ineko, Ikemura Kenji, Okuda Masahiro, et al.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 234-234
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pregnancy outcomes and mid-term prognosis in women after arterial switch operation for dextro-transposition of the great arteries - Tertiary hospital experiences and review of literature2019
Author(s)
Horiuchi C, Kamiya CA, Ohuchi H, Miyoshi T, Tsuritani M, Iwanaga N, Neki R, Niwa K, Kurosaki K, Ichikawa H, Ikeda T, Yoshimatsu J.
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Journal Title
J Cardiol
Volume: 73
Issue: 3
Pages: 247-54
DOI
Related Report
Peer Reviewed
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[Journal Article] Plasma natriuretic peptide levels in fetuses with congenital heart defect and arrhythmia: a single-center prospective study.2017
Author(s)
Miyoshi T, Umekawa T, Hosoda H, Asada T, Fujiwara A, Kurosaki KI, Shiraishi I, Nakai M, Nishimura K, Miyazato M, Kangawa K, Ikeda T, Yoshimatsu J, Minamino N.
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Journal Title
Ultrasound Obstet Gynecol.
Volume: 印刷中
Issue: 5
Pages: 609-16
DOI
Related Report
Peer Reviewed
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[Presentation] Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study.2019
Author(s)
Miyoshi T, Oku H, Asahara S, Okamoto A, Kokame K, Nakai M, Nishimura K, Otsuka F, Higashiyama A, Yoshimatsu J, Miyata T.
Organizer
Congress of International Society on Thrombosis and Hemostasis
Related Report
Int'l Joint Research
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[Book] 心エコー2018
Author(s)
三好剛一、根木玲子
Total Pages
304
Publisher
文光堂
Related Report
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