Selenoprotein P, a liver-derived secretory protein, regulates pressure overload-induced cardiac remodeling

• Project/Area Number: 15K09135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kanazawa University
• Principal Investigator: Usui Soichiro 金沢大学, 附属病院, 助教 (50507043)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心臓リモデリング / 心不全 / 心肝連関 / ヘパトカイン / 心肥大 / マイクロアレイ / 肝臓

Outline of Final Research Achievements

Selenoprotein P (SeP) is a liver-derived secretory protein that impairs insulin signal transduction and induces insulin resistance and hyperglycemia. Although clinical studies suggest the insulin resistance is an independent risk factor of heart failure, the role of SeP in pathogenesis of chronic heart failure is not well understood. We investigated the role of SeP in the regulation of cardiac remodeling in response to pressure overload. Transverse aortic constriction (TAC) was subjected to SeP knockout (KO) and wild-type (WT) mice for 2 weeks. The mortality rate following TAC was significantly decreased in SeP KO mice compared to WT mice. LV weight/body weight (BW) and Lung weight/BW were significantly smaller in SeP KO mice than in WT mice. Furthermore, mRNA expression of collagen 1a1 significantly less in SeP KO compared to WT. These results suggest that the absence of endogenous SeP attenuated cardiac hypertrophy, dysfunction and fibrosis in response to pressure overload in mice

Research Products

• [Journal Article] Endogenous Selenoprotein P, a Liver-Derived Secretory Protein, Mediates Myocardial Ischemia/Reperfusion Injury in Mice. (2018)
  • Author(s): Chikata A, Kato T, Usuda K, Fujita S, Maruyama M, Nagata Y, Sakagami S, Kanamori N, Yaegashi T, Saeki T, Kusayama T, Usui S, Furusho H, Kaneko S, Takamura M.
  • Journal Title: Int J Mol Sci. Volume: 19 Issue: 3 Pages: 878-878
  • DOI: 10.3390/ijms19030878
  • Peer Reviewed / Open Access
• [Journal Article] Augmented sphingosine 1 phosphate receptor-1 signaling in cardiac fibroblasts induces cardiac hypertrophy and fibrosis through angiotensin II and interleukin-6. (2017)
  • Author(s): Ohkura SI, Usui S, Takashima SI, Takuwa N, Yoshioka K, Okamoto Y, Inagaki Y, Sugimoto N, Kitano T, Takamura M, Wada T, Kaneko S, Takuwa Y.
  • Journal Title: PLoS One. Volume: 12 Issue: 8 Pages: e0182329-e0182329
  • DOI: 10.1371/journal.pone.0182329
  • Peer Reviewed / Open Access
• [Journal Article] β-Cryptoxanthin exerts greater cardioprotective effects on cardiac ischemia-reperfusion injury than astaxanthin by attenuating mitochondrial dysfunction in mice (2017)
  • Author(s): Pongkan Wanpitak、Takatori Osamu、Ni Yinhua、Xu Liang、Nagata Naoto、Chattipakorn Siriporn C.、Usui Soichiro、Kaneko Shuichi、Takamura Masayuki、Sugiura Minoru、Chattipakorn Nipon、Ota Tsuguhito
  • Journal Title: Mol Nutr Food Res. Volume: 61 Issue: 10 Pages: 1601077-1601077
  • DOI: 10.1002/mnfr.201601077
  • Peer Reviewed / Open Access
• [Journal Article] Long-Term Administration of Eicosapentaenoic Acid Improves Post-Myocardial Infarction Cardiac Remodeling in Mice by Regulating Macrophage Polarization. (2017)
  • Author(s): Takamura M, Kurokawa K, Ootsuji H, Inoue O, Okada H, Nomura A, Kaneko S, Usui S.
  • Journal Title: J Am Heart Assoc Volume: 21 Issue: 2
  • DOI: 10.1161/jaha.116.004560
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response. (2016)
  • Author(s): Takatori O, Usui S, Okajima M, Kaneko S, Ootsuji H, Takashima SI, Kobayashi D, Murai H, Furusho H, Takamura M.
  • Journal Title: J Cardiovasc Pharmacol Ther. Volume: 22 Issue: 3 Pages: 283-292
  • DOI: 10.1177/1074248416679308
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion. (2016)
  • Author(s): Takamura M, Usui S, Inoue O, Ootsuji H, Takashima SI, Nomura A, Kato T, Murai H, Furusho H, Sakai Y, Kaneko S.
  • Journal Title: Cardiol J Volume: 23 Issue: 6 Pages: 685-693
  • DOI: 10.5603/cj.a2016.0061
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Endogenous Selenoprotein P is a Positive Mediator of Cardiac Remodeling in Response to Pressure Overload (2017)
  • Author(s): Usui S
  • Organizer: The 81st Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Ishikawa Ongakudo, Kanazawa
  • Year and Date: 2017-03-17
  • Int'l Joint Research
• [Presentation] Endogenous selenoprotein P mediates pressure overload-induced cardiac hypertrophy (2017)
  • Author(s): Soichiro Usui
  • Organizer: ESC2017
  • Int'l Joint Research
• [Presentation] Muscle Specific E3 Ligase MAFbx Controls Cardiac Rupture after Myocardial Infarction in Mice (2016)
  • Author(s): Akio Chikata, Soichiro Usui、Shinichiro Takashima、Takeshi Kato、Hisayoshi Murai、Hiroshi Furusho、Shuichi Kaneko、Junichi Sadoshima、Masayuki Takamura
  • Organizer: 日本循環器学会 学術集会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-03-18
• [Presentation] Adipose Tissue-derived Stromal Cells Exert Beneficial Effect to Systemic Responses Following Myocardial Ischemia Reperfusion (2016)
  • Author(s): Soichiro Usui 、Oto Inoue、Shinichiro Takashima、Hiroshi Ohtsuji、Hisayoshi Murai、Shuichi Kaneko、Masayuki Takamura
  • Organizer: 日本循環器学会 学術集会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-03-18
• [Presentation] Endogenous MAFbx Mediates Cardiac Rupture After Myocardial Infarction in Mice (2015)
  • Author(s): Akio Chikata, Soichiro Usui
  • Organizer: AHA2015
  • Place of Presentation: USA フロリダ
  • Year and Date: 2015-11-07
  • Int'l Joint Research