Biomarkers of cardiac fibrosis in pressure overloaded heart.

• Project/Area Number: 15K08190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Kusakari Yoichiro 東京慈恵会医科大学, 医学部, 准教授 (80338889)
• Co-Investigator(Kenkyū-buntansha): 南沢 享 東京慈恵会医科大学, 医学部, 教授 (40257332) ; 岩本 武夫 東京慈恵会医科大学, 医学部, 准教授 (90568891)
• Research Collaborator: KUGA Kazuhiro ; YAMADA Yuki ; USUI Fumio
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 線維化 / 圧負荷 / 心臓線維化 / 心臓肥大 / バイオマーカー

Outline of Final Research Achievements

We found that the expression level of FGF23 in cardiac hyptrophy with fibrosis was significantly stronger than that of cardiac hypertrophy without fibrosis. To investigate whether FGF23 was a key factor of cardiac fibrosis, we applied FGF23 on cardiac fibroblast. FGF23 did not show any changes. However, FGF23 tended to promote trans-differentiation of fibroblasts stimulated by TGF-β
These results indicate that FGF23 is identified as a novel fibrosis-related gene and may enhance the effect of cytokines (ex TGF-beta) in initiation of cardiac fibrosis.

Research Products

• [Journal Article] Distinct vascular remodeling pattern of adult rats with carotid-jugular shunt. (2018)
  • Author(s): Lü Ping、Jiao Qibin、Shimura Daisuke、Kusakari Yoichiro、Liu Fang、Minamisawa Susumu
  • Journal Title: Annals of Vascular Surgery Volume: Epub ahead of print Pages: 168-178
  • DOI: 10.1016/j.avsg.2017.12.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The effects of heat stress on morphological properties and intracellular signaling of denervated and intact soleus muscles in rats (2017)
  • Author(s): Ohira Takashi、Higashibata Akira、Seki Masaya、Kurata Yoichi、Kimura Yayoi、Hirano Hisashi、Kusakari Yoichiro、Minamisawa Susumu、Kudo Takashi、Takahashi Satoru、Ohira Yoshinobu、Furukawa Satoshi
  • Journal Title: Physiol Rep Volume: 5 Issue: 15 Pages: e13350-e13350
  • DOI: 10.14814/phy2.13350
  • NAID: 120007134851
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary hypertension due to left heart disease causes intrapulmonary venous arterialization in rats (2017)
  • Author(s): Fujimoto Y, Urashima T, Kawachi F, Akaike T, Kusakari Y, Ida H, Minamisawa S
  • Journal Title: J Thorac Cardiovasc Surgy Volume: 154 Issue: 5 Pages: 1742-1753
  • DOI: 10.1016/j.jtcvs.2017.06.053
  • Peer Reviewed
• [Journal Article] Impairment of excitation-contraction coupling in right ventricular hypertrophied muscle with fibrosis induced by pulmonary artery banding. (2016)
  • Author(s): Kusakari Y, Urashima T, Shimura D, Amemiya E, Miyasaka G, Yokota S, Fujimoto Y, Akaike T, Inoue T, Minamisawa S．
  • Journal Title: PLoS One. Volume: 12 Issue: 1 Pages: e0169564-e0169564
  • DOI: 10.1371/journal.pone.0169564
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tissue thrombin is associated with the pathogenesis of dilated cardiomyopathy. (2016)
  • Author(s): Ito K, Hongo K, Date T, Ikegami M, Hano H, Owada M, Morimoto S, Kashiwagi Y, Katoh D, Yoshino T, Yoshii A, Kimura H, Nagoshi T, Kajimura I, Kusakari Y, Akaike T, Minamisawa S, Ogawa K, Minai K, Ogawa T, Kawai M, Yajima J, Matsuo S, Yamane T, Taniguchi I, Morimoto S, Yoshimura M.
  • Journal Title: Int J Cardiol. Volume: 228 Pages: 821-827
  • DOI: 10.1016/j.ijcard.2016.11.176
  • Peer Reviewed / Open Access
• [Journal Article] New mouse model of skeletal muscle atrophy using spiral wire immobilization (2016)
  • Author(s): Onda A, Kono H, Jiao Q, Akimoto T, Miyamoto T, Sawada Y, Suzuki K, Kusakari Y, Minamisawa S, Fukubayashi T
  • Journal Title: Muscle Nerve Volume: 54 Issue: 4 Pages: 788
  • DOI: 10.1002/mus.25202
  • Peer Reviewed / Open Access
• [Journal Article] Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats. (2016)
  • Author(s): Fujimoto Y, Urashima T, Shimura D, Ito R, Kawachi S, Kajimura I, Akaike T, Kusakari Y, Fujiwara M, Ogawa K, Goda N, Ida H, Minamisawa S
  • Journal Title: PLoS One Volume: 11(2) Issue: 2 Pages: e0148666-e0148666
  • DOI: 10.1371/journal.pone.0148666
  • Peer Reviewed / Open Access
• [Journal Article] Heterozygous deletion of sarcolipin maintains normal cardiac function. (2015)
  • Author(s): Shimura D, Kusakari Y, Sasano T, Nakashima Y, Nakai G, Jiao Q, Jin M, Yokota T, Ishikawa Y, Nakano A, Goda N, Minamisawa S.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 310(1) Issue: 1 Pages: 92-103
  • DOI: 10.1152/ajpheart.00411.2015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Diastolic overstretch enhanced the gene expression of fibrosis-related factors in isolated rat papillary muscle (2018)
  • Author(s): Kusakari Y
  • Organizer: 第95回日本生理学会学術集会
• [Presentation] 乳頭筋過伸展による線維化関連因子の発現変化とミトコンドリア内部の崩壊 (2017)
  • Author(s): 碓井文雄, 草刈洋一郎, 南沢享.
  • Organizer: 筋生理の集い
• [Presentation] 乳頭筋過伸展による線維化関連因子の発現変化. (2017)
  • Author(s): 草刈洋一郎
  • Organizer: 第247回東京談話会
• [Presentation] Diastolic overstretch of isolated rat papillary muscle reduced force development and increased gene expression of fibrosis-related factors (2017)
  • Author(s): Usui F, Yamada Y, Kusakari Y, Minamisawa S.
  • Organizer: 第134回成医会総会.
• [Presentation] Gene expression of fibrosis-related factors in isolated rat papillary muscle with diastolic overstretch (2017)
  • Author(s): Usui F, Yamada Y, Kusakari Y, Minamisawa S.
  • Organizer: 第94回日本生理学会学術集会
• [Presentation] FGF23 promote cardiac fibrosis by activating FGFR1 in presence of TGF-beta stimulation. (2016)
  • Author(s): Kuga K, Kusakari Y, Akaike T, Minamisawa S.
  • Organizer: 第33回国際心臓研究学会日本部会(ISHR2016).
  • Place of Presentation: 東京コンベンションホール
  • Year and Date: 2016-12-16
  • Int'l Joint Research
• [Presentation] FGF23によるTGF-betaを介した心臓線維化促進効果. (2016)
  • Author(s): 久我和寛、草刈洋一郎、南沢享.
  • Organizer: 心血管膜輸送研究会2016 「心血管膜輸送分子の構造・機能・病態の統合的研究戦略」
  • Place of Presentation: 九州大学
  • Year and Date: 2016-10-24
• [Presentation] Low output leads hepatic fibrosis in right heart failure model rats. (2016)
  • Author(s): Fujimoto Y, Urashima T, Shimura D, Ito R, Kajimura I, Akaike T, Kusakari Y, Goda N, Ida H, Minamisawa S
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-24
• [Presentation] Vitamin B1 pretreatment preserves cardiac function against ischemia-reperfusion injury. (2016)
  • Author(s): Yamada Y, Akaoka M, Watanabe M, Kasai Y, Kusakari Y, Minamisawa S.
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] Effects of heat stimulus on skeletal muscle properties. (2016)
  • Author(s): Ohira T, Sudoh M, Kusakari Y, Minamisawa S.
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] 長期宇宙滞在に伴う宇宙飛行士の骨格筋機能低下に対する予防策として温熱刺激の有効性の検討. (2015)
  • Author(s): 大平宇志、須藤正道、草刈洋一郎、南沢享.
  • Organizer: 筋生理の集い
  • Place of Presentation: 東京
  • Year and Date: 2015-12-19
• [Presentation] ビタミンB1の虚血再灌流における心保護メカニズム. (2015)
  • Author(s): 笠井裕平、山田祐揮、赤岡宗紀、渡邉政人、草刈洋一郎、南沢 享.
  • Organizer: 第132回成医会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-08
• [Presentation] Vitamin B1 preserves cardiac function against ischemia-reperfusion injury. (2015)
  • Author(s): Kasai Y, Yamada Y, Ikegami T, Kudo Y, Kusakari Y, Matsui T, Minamisawa S.
  • Organizer: Biomedical Sciences and Health Disparities Symposium.
  • Place of Presentation: Honolulu. Hawaii. USA.
  • Year and Date: 2015-04-05
  • Int'l Joint Research
• [Remarks] 東京慈恵会医科大学 細胞生理学講座
  • URL: http://www.jikei.ac.jp/academic/course/04_saiboseiri.html
• [Remarks] 東京慈恵会医科大学 細胞生理学講座 宇宙航空医学研究室
  • URL: http://sminamis.m38.coreserver.jp/Jikei_Cell_Physiology/Welcome.html