Matsushita-Mutoh Akiko

写真a

Title

Assistant Professor

Researcher Number(JSPS Kakenhi)

50570181

Current Affiliation Organization 【 display / non-display

  • Duty   University of the Ryukyus   Graduate School of Medicine   Assistant Professor  

University 【 display / non-display

  • 1992.04
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    1998.03

    Kitasato University     Graduated

External Career 【 display / non-display

  • 2009.03
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    2011.03

    University of the Ryukyus, Graduate School of Medicine, Research Associate  

  • 2011.04
     
     

    University of the Ryukyus, Graduate School of Medicine, Assistant Professor  

Affiliated academic organizations 【 display / non-display

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    American Heart Association 

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    The Japanese Onco-Cardiology Society 

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    The Japanese Circulation Society 

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    The Japanese Society of Hypertension 

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    The Japanese Society of Clinical Pharmacology and Therapeutics 

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Research Interests 【 display / non-display

  • Endothelial function

  • Cardiovascular medicine

  • 心血管細胞生物学

  • 臨床薬理学

  • 高血圧

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Research Areas 【 display / non-display

  • Life Science / Pharmacology

  • Life Science / Cardiology

Thesis 【 display / non-display

  • Mineralocorticoid Receptor-Mediated Endothelial Function

    2008.03

Published Papers 【 display / non-display

  • Effects of Low-Dose Colchicine on Serum High-Sensitivity C-Reactive Protein Level in Coronary Artery Disease Patients with Type 2 Diabetes Mellitus and Enhanced Inflammatory Response Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase 2, Dose-Finding Study

    Yoshikazu Miwa, Akiko Mutoh, Takeshi Morimoto, Yumi Ikehara, Takanori Yasu, Shinji Koba, Junya Ako, Yukihito Higashi, Masato Kajikawa, Hiroki Uehara, Kazuo Ishikawa, Ichiro Sakuma, Hirofumi Tomiyama, Koichi Node, Yuji Kumagai, Shinichiro Ueda

    Biomedicine Hub ( S. Karger AG )    156 - 164   2022.12 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    Although cardiovascular mortality in Japan is lower than in other industrialized countries, clinical outcomes in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM) remain poor despite multiple evidence-based drug therapies and interventions. We assumed that part of residual risk in these patients may be attributable to enhanced inflammation, which can be inhibited presumably by colchicine. However, dose-responsiveness of anti-inflammatory effect of colchicine has not been elucidated. Therefore, we designed a multicenter, randomized, double-blinded, parallel-group study to explore the dose-dependent effects of low-dose colchicine on serum high-sensitivity C-reactive protein (hs-CRP) concentration and safety in CAD patients with T2DM and enhanced inflammatory response as a phase 2 study. Enhanced inflammatory response was defined as peripheral white-blood cell count ≥7,000/μL. Patients (<i>N</i> = 63) will be randomly assigned to two doses of colchicine 0.25 mg/day, 0.5 mg/day, or placebo in a 1:1:1 ratio once daily for 12 weeks. Changes in serum hs-CRP levels will be evaluated as the primary endpoint, and changes in flow-mediated vasodilation and plasma myeloperoxidase levels will be evaluated as secondary endpoints. The results of this study will contribute to the development of a protocol for a planned future phase 3 trial to estimate the reduction in CAD. The present study describes the rationale, design, and methods of the trial.

  • Effect of Short-term Colchicine Treatment on Endothelial Function in Patients with Coronary Artery Disease

    Kajikawa M, Higashi Y, Tomiyama H, Maruhashi T, Kurisu S, Kihara Y, Mutoh A, Ueda SI

    International Journal of Cardiology   281   35 - 39   2019.04 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

  • Renin-angiotensin system inhibitors can prevent intravenous lipid infusion-induced myocardial microvascular dysfunction and leukocyte activation

    Takanori Yasu, Akiko Mutoh, Hiroshi Wada, Mayumi Kobayashi, Yuji Kikuchi, Shinichi Momomura, Shinichiro Ueda

    Circulation Journal ( Japanese Circulation Society )  82 ( 2 ) 494 - 501   2018 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    Background: Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS. Methods and Results: Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE). Leukocyte activity and hemorheology were also assessed ex vivo using a microchannel flow analyzer, serum levels of oxidative stress markers, and IκB-α expression in mononuclear cells. Serum FFA elevation by the infusion of lipid/heparin significantly decreased myocardial capillary blood velocity and myocardial blood flow during hyperemia. Both candesartan and perindopril significantly prevented the FFA-induced decrease in capillary blood velocity and myocardial blood flow during hyperemia. Systemic FFA loading also caused an increase in the number of adherent leukocytes and prolonged the whole blood passage time. These effects were blocked completely by candesartan and partially by perindopril. Both agents prevented the FFA-induced enhancement of oxidative stress and IκB-α degradation in mononuclear cells. Conclusions: Both candesartan and perindopril can prevent FFA-induced myocardial microcirculatory dysfunction during hyperemia via modulation of leukocyte activation and microvascular endothelial function.

  • Effects of Oral Antidiabetic Drugs on Changes in the Liver-to-Spleen Ratio on Computed Tomography and Inflammatory Biomarkers in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

    Koichi Yabiku, Akiko Mutoh, Kazufumi Miyagi, Nobuyuki Takasu

    CLINICAL THERAPEUTICS ( ELSEVIER )  39 ( 3 ) 558 - 566   2017.03 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    Purpose: Oral antidiabetic drugs (OADs) such as pioglitazone and metformin have beneficial effects in patients with nonalcoholic steatohepatitis. We prospectively assessed the effects of OADs on nonalcoholic fatty liver disease (NAFLD) in 886 men with type 2 diabetes mellitus and in a murine model of NAFLD. Methods: Patients were randomized to receive pioglitazone, metformin, sitagliptin, or a non-OAD (control) for 6 months. All the patients received dietary and exercise guidance once a month during this study. Changes in the liver-to-spleen ratio on computed tomography (CT) and NAFLD-related parameters were measured from baseline to the end of treatment. Findings: The liver/spleen ratio improved significantly in the pioglitazone and metformin groups compared with the control group (both P < 0.01), but not in the sitagliptin group (P = 0.73). The mean changes from baseline were -3.464 +/- 10.15 6%, 19.236 +/- 9.896%, 4.783 +/- 1.467%, and 1.328 0.802% in the control, pioglitazone, metformin, and sitagliptin groups, respectively. Multivariable analysis showed that the liver/spleen ratio was strongly correlated with high-sensitivity C-reactive protein concentration in the pioglitazone group (F = 9.973; P < 0.01) and abdominal visceral fat volume in the metformin group (F = 6.049; P < 0.05). Conclusions: Pioglitazone elicited the greatest improvements in features of NAFLD in type 2 diabetes mellitus. (C) 2017 Elsevier HS Journals, Inc. All rights reserved.

  • Peroxidized unsaturated fatty acids stimulate Toll-like receptor 4 signaling in endothelial cells

    Akiko Mutoh, Shinichiro Ueda

    LIFE SCIENCES ( PERGAMON-ELSEVIER SCIENCE LTD )  92 ( 20-21 ) 984 - 992   2013.05 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    Aim: Although unsaturated fatty acids are assumed to be protective against inflammatory disorders that include a pathway involving Toll-like receptor 4 (TLR4) activation, they might actually be toxic because of their high susceptibility to lipid peroxidation. Here we studied the effects of peroxidized unsaturated fatty acids on the TLR4-nuclear factor (NF)-kappa B pathway in endothelial cells. Main methods: Confluent cultured endothelial cells from bovine aorta were incubated for 1 h with fatty acids integrated into phosphatidylcholine vesicles. Lipopolysaccharide (LPS) or phosphatidylcholine vesicles without fatty acids were also applied as a positive control or a control for fatty acid groups, respectively. Activation of TLR4 and downstream signaling was assessed by membrane fractionation and Western blotting or immunofluorescent staining. Key findings: In the same way as LPS, application of sufficiently peroxidized unsaturated fatty acids like oleic acid or docosahexaenoic acid, acutely caused TLR4 translocation to caveolae/raft membranes, leading to activation of NF-kappa B signaling in endothelial cells. In contrast, saturated fatty acids did not show such effects. Applying well-peroxidized unsaturated fatty acids, but not saturated fatty acids, acutely activates the TLR4/NF-kappa B pathway. Significance: Peroxidation of unsaturated fatty acid is essential for the acute activation of TLR4 by the fatty acids that follow the same pathway as the activation by LPS. Unsaturated fatty acids have been assumed to be protective against inflammatory disorders, and drugs containing unsaturated fatty acids are now developed and provided. Our result suggests that, for inflammatory disorders involving TLR4 signaling, using unsaturated fatty acids as anti-inflammatory drugs may cause contrary effects. (C) 2013 Elsevier Inc. All rights reserved.

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Books 【 display / non-display

  • Medicine and Drug Journal

    Mutoh Akiko ( Part: Multiple Authorship )

    2018.12

Other Papers 【 display / non-display

  • Anti-atherosclerotic therapy by blocking leukocytes activity

    Akiko Mutoh-Matsushita

    Recent Advances in Clinical Pharmacology   ( 40 ) 193 - 198   2019.05

     

  • Micropartieles from Endothelial Cells Serve as Circulating NO Donor

    Akiko Mutoh, Shinichiro Ueda

    CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  128 ( 22 )   2013.11  [Refereed]

     

  • The Importance of Lipid Peroxidation in TLR4 Activation by Fatty Acids in Endothelial Cells

    Akiko Mutoh-Matsushita, Shinichiro Ueda

    CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  124 ( 21 )   2011.11  [Refereed]

     

  • Low-dose Eplerenone Down-regulates Caveolin-1 and Improves Endothelial Function by Mechanisms Independent of MR Antagonism

    Akiko Mutoh, Mitsuhiro Nishimoto, Masashi Isshiki, Toshiro Fujita

    CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  118 ( 18 ) S366 - S366   2008.10  [Refereed]

     

  • Imaging of bradykinin-induced Ca2(+) increase and NO production enhanced by ACE inhibitor, temocaprilat

    M Isshiki, F Taki, A Mutoh, K Yamamoto, J Ando, T Fujita

    HYPERTENSION ( LIPPINCOTT WILLIAMS & WILKINS )  42 ( 3 ) 436 - 436   2003.09  [Refereed]

     

Presentations 【 display / non-display

  • Microparticles from Endothelial Cells Serve as Circulating NO Donor

    Akiko Mutoh

    AHA Scientific Sessions  2013  -  2013 

  • The Importance of Lipid Peroxidation in TLR4 Activation by Fatty Acids in Endothelial Cells

    Akiko Mutoh-Matsushita and Shinichiro Ueda

    Circulation (Supplement)  2012  -  2012 

  • Blood cells’ RhoA is transcellularly delivered via microparticles to endothelial cells to get activated therein

    Akiko Mutoh

    International society of hypertension (ISH)  2012  -  2012 

  • The Importance of Lipid Peroxidation in TLR4 Activation by Fatty Acids in Endothelial Cells

    Akiko Mutoh-Matsushita

    Circulation (Supplement)  2012  -  2012 

  • The Importance of Lipid Peroxidation in TLR4 Activation by Fatty Acids in Endothelial Cells

    Akiko Mutoh

    AHA Scientific Sessions  2011  -  2011 

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Academic Awards 【 display / non-display

  • Travel Award for Young Investigators

    2013   AHA Council on ATVB  

    Winner: Matsushita-Mutoh Akiko

  • Travel Grant Award

    2008   International Society of Hypertension  

    Winner: Matsushita-Mutoh Akiko

Other External funds 【 display / non-display

  • Project Year: 2011  -  2011 

    Direct: 0 (YEN)  Overheads: 0 (YEN)  Total: 250,000 (YEN)

  • Project Year: 2011  -  2011 

    Member: Akiko Mutoh-Matsushita 

    Direct: 0 (YEN)  Overheads: 0 (YEN)  Total: 150,000 (YEN)

Social Activity 【 display / non-display

  • 2019.07
     
     

  • Horse manager

    2018.07
     
     

  • Horse manager

    2017.10