2021/12/04 更新

写真a

スギヤマ アキラ
杉山 彰
SUGIYAMA Akira
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 分子細胞医学専攻 シグナル伝達 助教
職名
助教
外部リンク

学位

  • 博士(獣医学) ( 2021年3月 )

研究分野

  • ライフサイエンス / 薬理学

  • ライフサイエンス / 獣医学

経歴(researchmap)

  • 新潟大学   大学院医歯学総合研究科 薬理学分野   助教

    2021年4月 - 現在

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  • 独立行政法人日本学術振興会   特別研究員-DC1

    2018年4月 - 2021年3月

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経歴

  • 新潟大学   教育研究院 医歯学系 医学系列   助教

    2021年4月 - 現在

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 シグナル伝達   助教

    2021年4月 - 現在

学歴

  • 北里大学   大学院獣医学系研究科   獣医学専攻

    2017年4月 - 2021年3月

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  • 北里大学   獣医学部   獣医学科

    2011年4月 - 2017年3月

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所属学協会

 

論文

  • Preventive Effect of Canstatin against Ventricular Arrhythmia Induced by Ischemia/Reperfusion Injury: A Pilot Study. 国際誌

    Akira Sugiyama, Yurie Shimizu, Muneyoshi Okada, Kosuke Otani, Hideyuki Yamawaki

    International journal of molecular sciences   22 ( 3 )   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ventricular arrhythmia induced by ischemia/reperfusion (I/R) injury is a clinical problem in reperfusion therapies for acute myocardial infarction. Ca2+ overload through reactive oxygen species (ROS) production is a major cause for I/R-induced arrhythmia. We previously demonstrated that canstatin, a C-terminal fragment of type IV collagen α2 chain, regulated Ca2+ handling in rat heart. In this study, we aimed to clarify the effects of canstatin on I/R-induced ventricular arrhythmia in rats. Male Wistar rats were subjected to I/R injury by ligating the left anterior descending artery followed by reperfusion. Ventricular arrhythmia (ventricular tachycardia and ventricular fibrillation) was recorded by electrocardiogram. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity and ROS production in neonatal rat cardiomyocytes (NRCMs) stimulated with oxygen glucose deprivation/reperfusion (OGD/R) were measured by lucigenin assay and 2',7'-dichlorodihydrofluorescein diacetate staining, respectively. The H2O2-induced intracellular Ca2+ ([Ca2+]i) rise in NRCMs was measured by a fluorescent Ca2+ indicator. Canstatin (20 µg/kg) inhibited I/R-induced ventricular arrhythmia in rats. Canstatin (250 ng/mL) inhibited OGD/R-induced NOX activation and ROS production and suppressed the H2O2-induced [Ca2+]i rise in NRCMs. We for the first time demonstrated that canstatin exerts a preventive effect against I/R-induced ventricular arrhythmia, perhaps in part through the suppression of ROS production and the subsequent [Ca2+]i rise.

    DOI: 10.3390/ijms22031004

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  • [Development of basic research toward clinical application of cleaved fragment of type IV collagen].

    Akira Sugiyama, Muneyoshi Okada, Kosuke Otani, Hideyuki Yamawaki

    Nihon yakurigaku zasshi. Folia pharmacologica Japonica   156 ( 5 )   282 - 287   2021年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Basement membrane is a dense sheet-like extracellular matrix (ECM), which separates cells from surrounding interstitium. Type IV collagen is a major component of basement membrane and three of six α chains (namely α1-α6 chains) form a triple-helix structure. Recently, endogenous bioactive factors called "matricryptins" or "matrikines", which are produced by degrading and cleaving C-terminal domain of type IV collagen, attract attentions as a novel therapeutic target or a candidate for biomarkers. In all type IV collagens, matricryptins called arresten (α1 chain), canstatin (α2), tumstatin (α3), tetrastatin (α4), pentastatin (α5), and hexastatin (α6), have been identified. The type IV collagen-derived matricryptins have been previously studied as new therapeutic targets for neoplastic diseases since they exert anti-angiogenic and/or anti-tumor effects. On the other hand, we have recently demonstrated the cardioprotective effects of matricryptins in addition to the altered expression levels in cardiac diseases. In this review, we introduce the results of fundamental studies for the type IV collagen-derived matricryptins in various diseases, such as neoplastic diseases and cardiac diseases, and discuss the potential clinical application as novel therapeutic agents and biomarkers.

    DOI: 10.1254/fpj.21016

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  • Decreased Expression of Canstatin in Rat Model of Monocrotaline-Induced Pulmonary Arterial Hypertension: Protective Effect of Canstatin on Right Ventricular Remodeling. 国際誌

    Akira Sugiyama, Maina Kaisho, Muneyoshi Okada, Kosuke Otani, Hideyuki Yamawaki

    International journal of molecular sciences   21 ( 18 )   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pulmonary arterial hypertension (PAH) is a progressive disease which causes right ventricular (RV) failure. Canstatin, a C-terminal fragment of type IV collagen α2 chain, is expressed in various rat organs. However, the expression level of canstatin in plasma and organs during PAH is still unclear. We aimed to clarify it and further investigated the protective effects of canstatin in a rat model of monocrotaline-induced PAH. Cardiac functions were assessed by echocardiography. Expression levels of canstatin in plasma and organs were evaluated by enzyme-linked immunosorbent assay and Western blotting, respectively. PAH was evaluated by catheterization. RV remodeling was evaluated by histological analyses. Real-time polymerase chain reaction was performed to evaluate RV remodeling-related genes. The plasma concentration of canstatin in PAH rats was decreased, which was correlated with a reduction in acceleration time/ejection time ratio and an increase in RV weight/body weight ratio. The protein expression of canstatin in RV, lung and kidney was decreased in PAH rats. While recombinant canstatin had no effect on PAH, it significantly improved RV remodeling, including hypertrophy and fibrosis, and prevented the increase in RV remodeling-related genes. We demonstrated that plasma canstatin is decreased in PAH rats and that administration of canstatin exerts cardioprotective effects.

    DOI: 10.3390/ijms21186797

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  • Long-term administration of recombinant canstatin prevents adverse cardiac remodeling after myocardial infarction. 国際誌

    Akira Sugiyama, Rumi Ito, Muneyoshi Okada, Hideyuki Yamawaki

    Scientific reports   10 ( 1 )   12881 - 12881   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Myocardial infarction (MI) still remains a leading cause of mortality throughout the world. An adverse cardiac remodeling, such as hypertrophy and fibrosis, in non-infarcted area leads to uncompensated heart failure with cardiac dysfunction. We previously demonstrated that canstatin, a C-terminus fragment of type IV collagen α2 chain, exerted anti-remodeling effect against isoproterenol-induced cardiac hypertrophy model rats. In the present study, we examined whether a long-term administration of recombinant canstatin exhibits a cardioprotective effect against the adverse cardiac remodeling in MI model rats. Left anterior descending artery of male Wistar rats was ligated and recombinant mouse canstatin (20 μg/kg/day) was intraperitoneally injected for 28 days. Long-term administration of canstatin improved survival rate and significantly inhibited left ventricular dilatation and dysfunction after MI. Canstatin significantly inhibited scar thinning in the infarcted area and significantly suppressed cardiac hypertrophy, nuclear translocation of nuclear factor of activated T-cells, interstitial fibrosis and increase of myofibroblasts in the non-infarcted area. Canstatin significantly inhibited transforming growth factor-β1-induced differentiation of rat cardiac fibroblasts into myofibroblasts. The present study for the first time demonstrated that long-term administration of recombinant canstatin exerts cardioprotective effects against adverse cardiac remodeling in MI model rats.

    DOI: 10.1038/s41598-020-69736-y

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  • Canstatin suppresses isoproterenol-induced cardiac hypertrophy through inhibition of calcineurin/nuclear factor of activated T-cells pathway in rats. 国際誌

    Akira Sugiyama, Muneyoshi Okada, Hideyuki Yamawaki

    European journal of pharmacology   871   172849 - 172849   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pathological cardiac hypertrophy associated with cardiac dysfunction is an independent risk factor for arrhythmia, myocardial infarction and sudden death. Canstatin, a C-terminal fragment of type IV collagen α2 chain, is abundantly expressed in normal heart tissue. We previously demonstrated that canstatin inhibits isoproterenol (ISO)-induced dephosphorylation of nuclear factor of activated T-cells (NFAT)c4, which plays an important role in cardiac hypertrophy, in differentiated H9c2 cardiomyoblasts. Thus, we investigated whether in vivo canstatin administration prevents ISO-induced cardiac hypertrophy through the inhibition of NFATc4 pathway. Rats were subcutaneously injected with ISO (5 mg/kg) or saline (Cont) for 7 days. Simultaneously, recombinant mouse canstatin (20 μg/kg) or vehicle was intraperitoneally administered. After left ventricular wall thickness and cardiac function were measured by echocardiography, the hearts were isolated and left ventricular weight (LVW) was weighed. Azan staining was performed to measure cross-sectional diameter of cardiomyocytes. Activity of calcineurin, which dephosphorylates NFATc4, was measured by calcineurin phosphatase activity assay. Immunohistochemical staining was performed to evaluate nuclear translocation of NFATc4. Intracellular Ca2+ concentration in neonatal rat cardiomyocytes (NRCMs) was measured by using a calcium indicator. Canstatin significantly inhibited ISO-induced increase of LVW, left ventricular posterior wall thickness at end-diastole and diameter of cardiomyocytes. Canstatin significantly inhibited ISO-induced activation of calcineurin, nuclear translocation of NFATc4, increased mRNA expression of β-myosin heavy chain and α-skeletal actin, and intracellular Ca2+ rise in NRCMs. In summary, we for the first time demonstrated that canstatin administration suppresses ISO-induced cardiac hypertrophy possibly through the blockade of calcineurin/NFATc4 pathway in rats.

    DOI: 10.1016/j.ejphar.2019.172849

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  • Cathepsin S degrades arresten and canstatin in infarcted area after myocardial infarction in rats.

    Akira Sugiyama, Ayaka Mitsui, Muneyoshi Okada, Hideyuki Yamawaki

    The Journal of veterinary medical science   81 ( 4 )   522 - 531   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The basement membrane surrounding cardiomyocytes is mainly composed of α1 and α2 chain of type IV collagen. Arresten and canstatin are fragments of non-collagenous C-terminal domain of α1 and α2 chain, respectively. We previously reported that the expression of canstatin was decreased in infarcted area 2 weeks after myocardial infarction in rats. In the present study, we investigated the regulatory mechanism for expression of arresten and canstatin. Myocardial infarction model rats were produced by ligating left anterior descending artery. Western blotting and immunohistochemical staining were performed to determine the protein expression and distribution. Arresten and canstatin were highly expressed in the heart. One day and three days after myocardial infarction, the expression of arresten and canstatin in infarcted area was lower than that in non-infarcted area. The expression of cathepsin S, which is known to degrade arresten and canstatin, was increased in the infarcted area. A knockdown of cathepsin S gene using small interference RNA suppressed the decline of arresten and canstatin in the infarcted area 3 days after myocardial infarction. This study for the first time revealed that arresten and canstatin are immediately degraded by cathepsin S in the infarcted area after myocardial infarction. These findings present a novel fundamental insight into the pathogenesis of myocardial infarction through the turnover of basement membrane-derived endogenous factors.

    DOI: 10.1292/jvms.18-0674

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  • Endostatin Stimulates Proliferation and Migration of Myofibroblasts Isolated from Myocardial Infarction Model Rats. 国際誌

    Akira Sugiyama, Yuka Hirano, Muneyoshi Okada, Hideyuki Yamawaki

    International journal of molecular sciences   19 ( 3 )   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Myofibroblasts contribute to the healing of infarcted areas after myocardial infarction through proliferation, migration, and production of extracellular matrix (ECM). Expression of endostatin, a cleaved fragment of type XVIII collagen, increases in the heart tissue of an experimental myocardial infarction model. In the present study, we examined the effect of endostatin on the function of myofibroblasts derived from an infarcted area. The myocardial infarction model was created by ligating the left anterior descending artery in rats. Two weeks after the operation, α-smooth muscle actin (α-SMA)-positive myofibroblasts were isolated from the infarcted area. Endostatin significantly increased the proliferation and migration of myofibroblasts in vitro. On the other hand, endostatin had no effect on the production of type I collagen, a major ECM protein produced by myofibroblasts. Endostatin activated Akt and extracellular signal-regulated kinase (ERK), and the pharmacological inhibition of these signaling pathways suppressed the endostatin-induced proliferation and migration. A knockdown of the COL18A1 gene in the myocardial infarction model rats using small interference RNA (siRNA) worsened the cardiac function concomitant with wall thinning and decreased the α-SMA-positive myofibroblasts and scar formation compared with that of control siRNA-injected rats. In summary, we demonstrated for the first time that endostatin might be an important factor in the healing process after myocardial infarction through the activation of myofibroblasts.

    DOI: 10.3390/ijms19030741

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  • Pathophysiological roles of canstatin on myofibroblasts after myocardial infarction in rats. 国際誌

    Akira Sugiyama, Muneyoshi Okada, Hideyuki Yamawaki

    European journal of pharmacology   807   32 - 43   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Myofibroblasts play an important role during remodeling process after myocardial infarction through proliferation, migration, production and degradation of extracellular matrix (ECM) and contraction. Canstatin, a 24kDa polypeptide, is cleaved from α2 chain of type IV collagen, which is a major component of basement membrane around cardiomyocytes. We examined the effects of canstatin on myofibroblasts isolated from the areas of myocardial infarction. Myocardial infarction model was made by ligating left anterior descending artery of Wistar rats. Two weeks after the operation, the cells were isolated by an explant method and identified as myofibroblasts with immunofluorescence staining. Cell counting assay was performed to examine cell proliferation. Boyden chamber assay was performed to examine cell migration. Expression and phosphorylation of proteins were detected by Western blotting. Collagen gel contraction assay was performed to measure cell contractility. Canstatin stimulated proliferation, secretion of matrix metalloproteinases, expression of cyclooxygenase (COX)-2, and inhibited collagen gel contraction in myofibroblasts. Canstatin increased Akt phosphorylation. LY294002, a phosphoinositide-3-kinase/Akt inhibitor, inhibited the canstatin-induced proliferation. NS-398, a COX-2 inhibitor, suppressed the inhibitory effect of canstatin on collagen gel contraction. Canstatin expression in areas of myocardial infarction 2 weeks after surgery decreased. We for the first time demonstrate that canstatin is an endogenous bioactive molecule regulating the various functions of myofibroblasts after myocardial infarction. The decrease of canstatin expression in the maturated areas of myocardial infarction might lead to stabilization of scar tissues perhaps in part through the reduction of proliferation and ECM degradation as well as the stimulation of contractility in myofibroblasts.

    DOI: 10.1016/j.ejphar.2017.04.027

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  • New Insights into the Role of Basement Membrane-Derived Matricryptins in the Heart.

    Muneyoshi Okada, Keisuke Imoto, Akira Sugiyama, Jumpei Yasuda, Hideyuki Yamawaki

    Biological & pharmaceutical bulletin   40 ( 12 )   2050 - 2060   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The extracellular matrix (ECM), which contributes to structural homeostasis as well as to the regulation of cellular function, is enzymatically cleaved by proteases, such as matrix metalloproteinases and cathepsins, in the normal and diseased heart. During the past two decades, matricryptins have been defined as fragments of ECM with a biologically active cryptic site, namely the 'matricryptic site,' and their biological activities have been initially identified and clarified, including anti-angiogenic and anti-tumor effects. Thus, matricryptins are expected to be novel anti-tumor drugs, and thus widely investigated. Although there are a smaller number of studies on the expression and function of matricryptins in fields other than cancer research, some matricryptins have been recently clarified to have biological functions beyond an anti-angiogenic effect in heart. This review particularly focuses on the expression and function of basement membrane-derived matricryptins, including arresten, canstatin, tumstatin, endostatin and endorepellin, during cardiac diseases leading to heart failure such as cardiac hypertrophy and myocardial infarction.

    DOI: 10.1248/bpb.b17-00308

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講演・口頭発表等

  • IV型コラーゲンα2鎖分解産物canstatinの血中濃度はモノクロタリン誘発ラット肺高血圧症モデルの重症度と相関する

    杉山 彰, 岡田 宗善, 大谷 紘資, 山脇 英之

    第163回日本獣医会学術集会  2020年9月 

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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:ポスター発表  

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  • Effects of canstatin, a fragment of type IV collagen α2 chain, on experimental models of arrhythmia in rats

    Akira Sugiyama, Yurie Shimizu, Muneyoshi Okada, Hideyuki Yamawaki

    Basic Cardiovascular Sciences 2020 Scientific Sessions  2020年7月 

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    開催年月日: 2020年7月

    記述言語:英語   会議種別:ポスター発表  

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  • IV型コラーゲンα1鎖分解断片arrestenは心線維芽細胞及び左心房筋の機能を調節する

    杉山 彰, 田嶋 志帆, 山本 理幾, 岡田 宗善, 大谷 紘資, 山脇 英之

    第94回日本薬理学会年会  2021年3月 

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    記述言語:英語   会議種別:ポスター発表  

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  • 圧負荷誘発心リモデリングにおいて保護作用を示すIV型コラーゲンα2鎖分解産物canstatinの活性部位の探索及びバイオマーカーとしての有用性の検討

    杉山 彰, 改正 茉侑奈, 岡田 宗善, 大谷 紘資, 山脇 英之

    第30回日本循環薬理学会  2020年11月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • IV型コラーゲンα2鎖C末端断片canstatinはラット虚血/再灌流誘導性心室性不整脈を抑制する

    清水 友里恵, 杉山 彰, 岡田 宗善, 山脇 英之

    第93回日本薬理学会年会  2020年3月 

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    記述言語:英語  

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  • IV型コラーゲン分解断片canstatinの心疾患における臨床応用を目指した基礎的検討

    杉山 彰, 改正 茉侑奈, 岡田 宗善, 山脇 英之

    第2回日本比較薬理学・毒性学会 春季研究会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • モノクロタリン誘発肺高血圧症モデルラットにおけるIV型コラーゲンα2鎖分解産物canstatinの右心肥大及び線維化抑制作用

    杉山 彰, 改正 茉侑奈, 岡田 宗善, 山脇 英之

    第29回日本循環薬理学会/第55回高血圧関連疾患モデル学会 合同学会  2019年11月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 心線維化及び心肥大を抑制するcanstatin活性部位の同定

    杉山 彰, 岡田 宗善, 山脇 英之

    第162回日本獣医学会学術集会  2019年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • IV型コラーゲンα2鎖分解産物canstatinの心線維化及び心筋肥大化抑制作用を担う活性部位の探索

    杉山 彰, 岡田 宗善, 山脇 英之

    第32回北里大学バイオサイエンスフォーラム  2019年8月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Cardioprotective effect of canstatin against myocardial infarction in rats

    Akira Sugiyama, Rumi Ito, Muneyoshi Okada, Hideyuki Yamawaki

    Basic Cardiovascular Sciences 2019 Scientific Sessions  2019年7月 

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    記述言語:英語   会議種別:ポスター発表  

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  • IV型コラーゲンα2鎖分解断片canstatinは心筋梗塞後の心不全を予防する

    杉山 彰, 岡田 宗善, 山脇 英之

    第92回日本薬理学会年会  2019年3月 

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    記述言語:英語   会議種別:口頭発表(一般)  

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  • 心筋梗塞及び心肥大モデルに対するリコンビナントcanstatin慢性投与による心保護作用

    杉山 彰, 岡田 宗善, 山脇 英之

    第1回日本比較薬理学・毒性学会 春季研究会  2019年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Canstatin, a fragment of type IV collagen α2 chain, inhibits isoproterenol-induced cardiac hypertrophy in rats

    Akira Sugiyama, Muneyoshi Okada, Hideyuki Yamawaki

    Joint Hypertension 2018 Scientific Sessions  2018年9月 

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    記述言語:英語   会議種別:口頭発表(一般)  

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  • IV型コラーゲン分解断片canstatinがイソプロテレノール誘発心肥大に及ぼす影響

    杉山 彰, 岡田 宗善, 山脇 英之

    第31回北里大学バイオサイエンスフォーラム  2018年8月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • ラット心筋梗塞後の病変形成におけるIV型コラーゲン分解産物canstatinの役割解明

    杉山 彰, 伊藤 瑠美, 岡田 宗善, 山脇 英之

    第30回北里大学バイオサイエンスフォーラム  2017年8月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Regulatory mechanism for expression of matricryptins after myocardial infarction in rats

    Akira Sugiyama, Ayaka Mitsui, Muneyoshi Okada, Hideyuki Yamawaki

    18th World Congress of Basic and Clinical Pharmacology  2017年7月 

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    記述言語:英語   会議種別:ポスター発表  

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  • Canstatinは心筋梗塞後の筋線維芽細胞機能を調節する

    杉山 彰, 岡田 宗善, 山脇 英之

    第90回日本薬理学会年会  2017年3月 

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    記述言語:英語   会議種別:口頭発表(一般)  

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  • ラット心筋梗塞モデル由来筋線維芽細胞機能に及ぼすcanstatinの影響

    杉山 彰, 岡田 宗善, 山脇 英之

    第159回日本獣医学会学術集会  2016年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Canstatinはラット心筋梗塞モデル由来筋線維芽細胞の増殖を促進する

    杉山 彰, 岡田 宗善, 山脇 英之

    第29回北里大学バイオサイエンスフォーラム  2016年8月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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受賞

  • 獣医学奨励賞

    2021年9月   公益社団法人 日本獣医学会  

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  • 大村賞

    2021年3月   学校法人北里研究所  

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  • 優秀演題賞

    2019年11月   第29回日本循環薬理学会/第55回高血圧関連疾患モデル学会 合同学会  

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共同研究・競争的資金等の研究

  • 胎児浮腫の原因遺伝子と予後を関連付けるマウスモデル研究基盤の確立

    研究課題/領域番号:21K20615  2021年8月 - 2023年3月

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    杉山 彰

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    配分額:3120000円 ( 直接経費:2400000円 、 間接経費:720000円 )

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  • Canstatin活性部位の同定と新規心疾患治療への応用

    研究課題/領域番号:18J20623  2018年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    杉山 彰

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    配分額:2800000円 ( 直接経費:2800000円 )

    Canstatinの活性部位同定と新規心疾患治療への応用を目指して検討を行い、以下の成果を得た。
    ①ラット心線維芽細胞及び新生仔ラット心筋細胞へのリコンビナントcanstatin断片処置実験を行い、N末端側のcanstatin断片(N-canstatin)がtransforming growth factor-β誘導性Smad2及び extracellular signal regulated kinaseリン酸化の抑制を介して心線維芽細胞の筋線維芽細胞への分化を抑制し、isoproterenol (ISO)誘導性新生仔ラット心筋細胞肥大を抑制することを明らかにした。②ISO誘発心肥大モデルラットに対する全長canstatinの慢性投与が、細胞内カルシウムイオン濃度上昇/カルシニューリン活性/nuclear factor of activated T cells核内移行/心肥大関連遺伝子の転写を抑制することで抗心肥大作用を示すことを明らかにした。③心筋梗塞モデルラットに対する全長canstatin慢性投与が梗塞領域の瘢痕菲薄化及び非梗塞領域の心肥大、線維化を抑制することで左室拡張及び機能低下を抑制することを明らかにした。④モノクロタリン誘発肺高血圧症ラットに対する全長canstatin慢性投与が右心肥大及び線維化を抑制することを明らかにした。⑤全長canstatin急性投与が虚血再灌流(I/R)誘発心室性不整脈モデルラットにおける心室細動の発生及び心室性不整脈の持続時間を低下することを明らかにした。⑥モノクローナル抗体を用いてcanstatinサンドイッチELISAキットを構築した。
    成果②は学術論文として公表し、①及び③~⑥は学会で発表した。

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