Pathophysiological significance of cathepsin K in dilated cardiomyopathy

• Project/Area Number: 25860594
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Nagoya University
• Principal Investigator: Okumura Takahiro 名古屋大学, 医学部附属病院, 助教 (60635598)
• Research Collaborator: MUROHARA TOYOAKI 名古屋大学, 医学系研究科, 教授 (90299503) ; BANDO YASUKO 名古屋大学, 医学部附属病院, 講師 (60452190) ; MORIMOTO RYOTA 名古屋大学, 医学系研究科, 寄附講座助教 (00755499)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 拡張型心筋症 / カテプシン

Outline of Final Research Achievements

To clarify the pathophysiological role of cathepsin K, we investigated the association between the expression of cathepsin K and pathophysiological index, clinical imaging data, or prognosis in patients with dilated cardiomyopathy (DCM). The results of our studies were as follows; 1) Myocardial fibrosis and impaired left ventricular (LV) relaxation is more serious in late gadolinium enhancement positive group. Unfortunately, the expression of cathepsin K was not associated with the extent of fibrosis. 2) LV phase entropy using 99mTc-sestamibi gated myocardial perfusion SPECT, which may reflect impairment of Ca2+-handling caused by decreased SERCA2a mRNA levels, is a novel prognostic predictor of adverse cardiac events in patients with DCM with a narrow QRS complex. 3) The combined reduction of campesterol and lathosterol that indicated intestinal cholesterol absorption and liver synthesis predicts future cardiac events in patients with early-stage DCM.

Research Products

• [Journal Article] Cardiopulmonary Exercise Testing as a Tool for Diagnosing Pulmonary Hypertension in Patients with Dilated Cardiomyopathy. (2016)
  • Author(s): Hirashiki A, Kondo T, Okumura T, Kamimura Y, Nakano Y, Fukaya K, Sawamura A, Morimoto R, Adachi S, Takeshita K, Murohara T.
  • Journal Title: Ann Noninvasive Electrocardiol. Volume: - Issue: 3 Pages: 263-271
  • DOI: 10.1111/anec.12308
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic impact of combined late gadolinium enhancement on cardiovascular magnetic resonance and peak oxygen consumption in ambulatory patients with nonischemic dilated cardiomyopathy. (2014)
  • Author(s): Yamada T, Hirashiki A, Okumura T, Adachi S, Shimazu S, Shimizu S, Morimoto R, Takeshita K, Naganawa S, Kondo T, Murohara T.
  • Journal Title: J Card Fail. Volume: 20 Issue: 11 Pages: 825-32
  • DOI: 10.1016/j.cardfail.2014.08.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prognostic value of pulmonary hypertension in ambulatory patients with non-ischemic dilated cardiomyopathy. (2014)
  • Author(s): Hirashiki A, Kondo T, Adachi S, Nakano Y, Shimazu S, Shimizu S, Morimoto R, Okumura T, Murohara T.
  • Journal Title: Circulation Journal Volume: 78(5) Pages: 1245-53
  • NAID: 130003391072
  • Peer Reviewed
• [Journal Article] Prognostic Value of Pulmonary Hypertension in Ambulatory Patients With Non-Ischemic Dilated Cardiomyopathy (2014)
  • Author(s): Hirashiki A, Kondo T, Adachi S, Nakano Y, Shimazu S, Shimizu S, Morimoto R, Okumura T, Murohara T.
  • Journal Title: Circulation Journal Volume: 78 Issue: 5 Pages: 1245-1253
  • DOI: 10.1253/circj.CJ-13-1120
  • NAID: 130003391072
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Increased 99m Tc-sestamibi Washout Reflects Impaired Myocardial Contractile and Relaxation Reserve during Dobutamine Stress Due to Mitochondrial Dysfunction in Dilated Cardiomyopathy Patients. (2013)
  • Author(s): Hayashi D, Ohshima S, Isobe S, Cheng XW, Unno K, Funahashi H, Shinoda N, Okumura T, Hirashiki A, Kato K, Murohara T.
  • Journal Title: J Am Coll Cardiol Volume: 1 Issue: 19 Pages: 1-2
  • DOI: 10.1016/j.jacc.2013.01.074
  • Peer Reviewed
• [Journal Article] Relationship of myocardial fibrosis to left ventricular and mitochondrial function in nonischemic dilated cardiomyopathy--a comparison of focal and interstitial fibrosis (2013)
  • Author(s): Yamada T, Hirashiki A, Cheng XW, Okumura T, Shimazu S, Okamoto R, Shinoda N, Isobe S, Takeshita K, Naganawa S, Kondo T, Murohara T
  • Journal Title: J Card Fail Volume: 8 Issue: 8 Pages: 557-64
  • DOI: 10.1016/j.cardfail.2013.05.018
  • Peer Reviewed
• [Journal Article] Assessment of cardiac contractile reserve. (2013)
  • Author(s): Okumura T, Shimizu S, Fukaya K, Sawamura A, Morimoto R, Shimazu S, Hirashiki A, Takeshita K, Bando YK, Murohara T.
  • Journal Title: Rinsho Byori. Volume: 61(10) Pages: 917-923
  • NAID: 40019854856
  • Peer Reviewed
• [Presentation] 重症心不全に対する内科医の戦略 (2016)
  • Author(s): 奥村貴裕，近藤徹，澤村昭典，平岩宏章，青木聡一郎，一居武夫，渡辺直樹，加納直明，古澤健司，深谷兼次，森本竜太，室原豊明
  • Organizer: 第24回日本集中治療医学会東海北陸地方会
  • Place of Presentation: ウインクあいち（愛知県名古屋市）
  • Year and Date: 2016-06-25
  • Invited
• [Presentation] Clinical Significance of Cholesterol Metabolism Impairment in Patients with Non-ischemic Dilated Cardiomyopathy (2016)
  • Author(s): Akinori Sawamura, Takahiro Okumura, Hiroaki Hiraiwa, Toru Kondo, Soichiro Aoki, Takeo Ichii, Kenji Furusawa, Naoki Watanabe, Naoaki Kanoh, Hiroaki Mori, Kenji Fukaya, Ryota Morimoto, Akihiro Hirashiki, Kyosuke Takeshita, Yasuko Bandoh, Toyoaki Murohara
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] Prognostic Value of Sphericity Index Assessed by Cardiac Magnetic Resonance in Patients with Dilated Cardiomyopathy (2016)
  • Author(s): Naoaki Kano, Takahiro Okumura, Hiroaki Hiraiwa, Toru Kondo, Naoki Watanabe, Kenji Fukaya, Soichiro Aoki, Takeo Ichii, Kenji Furusawa, Hiroaki Mori, Akinori Sawamura, Ryota Morimoto, Yasuko Bandoh, Toyoaki Murohara
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] Dobutamine Stress as a Predictor of Left Venrricular Reverse Remodeling in Dilated Cardiomyopathy (2016)
  • Author(s): Ryota Morimoto,Takeo Ichii, Soichiro Aoki, Kenji Furusawa, Hiroaki Mori, Hiroaki Hiraiwa, Toru Kondo, Naoki Watanabe, Naoaki Kanoh, Kenji Fukaya, Akinori Sawamura, Takahiro Okumura, Kyosuke Takeshita, Toyoaki Murohara
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] Electrocardiographic Changes of Left Ventricular Reverse Remodeling in Dilated Cardiomyopathy Patients (2015)
  • Author(s): Kenji Fukaya, Takahiro Okumura, Hiroaki Hiraiwa, Toru Kondo, Souichiro Aoki, Takeo Ichii, Kenji Furusawa, Naoki Watanabe, Naoaki Kano, Hiroaki Mori, Akinori Sawamura, Ryota Morimoto, Yasuko Bando, Toyoaki Murohara
  • Organizer: 第19回日本心不全学会総会
  • Place of Presentation: グランフロント大阪 ナレッジキャピタル コングレコンベンションセンター（大阪府大阪市）
  • Year and Date: 2015-10-22
• [Presentation] Aspect Ratio of Left Ventricle in Cardiac Magnetic Resonance Predicts a Future Reverse Remodeling in Non-ischemic Dilated Cardiomyopathy (2015)
  • Author(s): Naoaki Kano, Takahiro Okumura, Hiroaki Hiraiwa, Toru Kondo, Souichiro Aoki, Takeo Ichii, Kenji Furusawa, Naoki Watanabe, Hiroaki Mori, Kenji Fukaya, Akinori Sawamura, Ryota Morimoto, Yasuko Bando, Toyoaki Murohara
  • Organizer: 第19回日本心不全学会総会
  • Place of Presentation: グランフロント大阪 ナレッジキャピタル コングレコンベンションセンター（大阪府大阪市）
  • Year and Date: 2015-10-22
• [Presentation] Cardiomyocyte Porosity is a Novel Predictor of Left Ventricular Reverse Remodeling in Patient with Dilated Cardiomyopathy (2015)
  • Author(s): Kenji Fukaya, Takahiro Okumura, Naoki Watanabe, Naoaki Kanoh, Akinori Sawamura, Hiroaki Mori, Ryota Morimoto, Kyosuke Takeshita, Yasuko Bando, Toyoaki Murohara
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] Intra-Ventricular Contractile Entropy in 99mTc-Sestamibi gated SPECT is a Novel Prognostic Predictor in Patients with Non-ischemic Dilated Cardiomyopathy (2015)
  • Author(s): Naoaki Kano, Takahiro Okumura, Naoki Watanabe, Kenji Fukaya, Akinori Sawamura, Hiroaki Mori, Ryota Morimoto, Akihiro Hirashiki, Yasuko Bando, Toyoaki Murohara
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] Left Ventricular Contractile Entropy in 99mTc-Sestamibi SPECT is a Novel Prognostic Predictor in Patients with Non-ischemic Dilated Cardiomyopathy (2014)
  • Author(s): Naoaki Kano, Takahiro Okumura, Akinori Sawamura, Naoki Watanabe, Hiroaki Mori, Kenji Fukaya, Ryota Morimoto, Akinori Hirashiki, Yasuko Kureishi-Bando, Toyoaki Murohara
  • Organizer: 第18回 日本心不全学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-10-10 – 2014-10-12
• [Presentation] Prognostic value of alveolar diffusing capacity in patients with non-ischemic dilated cardiomyopathy (2014)
  • Author(s): Ryota Morimoto, Takahiro Okumura, Naoaki Kano, Naoki Watanabe, Tomoaki Mori, Kenji Fukaya, Akinori Sawamura, Kyosuke Takeshita, Yasuko Kureishi-Bando, Toyoaki Murohara
  • Organizer: 第18回 日本心不全学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-10-10 – 2014-10-12
• [Presentation] Blood pressure alterations during heart failure treatment in patients with non-ischemic dilated cardiomyopathy (2014)
  • Author(s): Akinori Sawamura, Takahiro Okumura, Kenji Fukaya, Ryota Morimoto, Shinya Shimizu, Shuzo Shimazu, Akihiro Hirashiki, Kyosuke Takeshita, Yasuko Bando, Toyoaki Murohara
  • Organizer: ESC Congress 2014
  • Place of Presentation: Congress centre Fira Gran Via (Barcelona, Spain)
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Circadian Blood Pressure Pattern; A Novel Prognostic Marker in Non-ischemic Dilated Cardiomyopathy (2014)
  • Author(s): A. Sawamura, T. Okumura, K. Fukaya, S. Shimizu, R. Morimoto, S. Shimazu, A. Hirashiki, K. Takeshita, Y. Bando, T. Murohara
  • Organizer: 7th Asia Pacific Congress of Heart Failure
  • Place of Presentation: Bali Nusa Dua Convention Center, (Indonesia)
  • Year and Date: 2014-04-17 – 2014-04-19
• [Presentation] Left Ventricular Function and Functional Reserve in Obese and Underweight Patients with Dilated Cardiomyopathy. (2014)
  • Author(s): Takahiro Okumura, Kenji Fukaya, Akinori Sawamura, Ryota Morimoto, Shinya Shimizu, Shuzo Shimazu, Akihiro Hirashiki, Kyosuke Takeshita, Yasuko Bando, Toyoaki Murohara.
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム （東京都千代田区）
• [Presentation] Incremental Prognostic Value of Myocardial Contractile Reserve to Cardiac Sympathetic Function in Patients with Dilated Cardiomyopathy. (2014)
  • Author(s): Kenji Fukaya, Satoshi Isobe, Takahiro Okumura, Akinori Sawamura, Ryota Morimoto, Shinya Shimizu, Akihiro Hirashiki, Kyosuke Takesita, Yasuko Bando, Toyoaki Murohara.
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム （東京都千代田区）
• [Presentation] 拡張型心筋症における最大酸素摂取量は，心収縮予備能を反映し，逆リモデリング・予後予測に有用である． (2013)
  • Author(s): 奥村貴裕, 清水真也, 平敷安希博, 河野裕治, 竹下享典, 山田純生, 室原豊明
  • Organizer: 第19回日本心臓リハビリテーション学会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
• [Presentation] Relation between myocardial contractile reserve and exercise capacity in prognosis of non-ischemic dilated cardiomyopathy. (2013)
  • Author(s): Shinya Shimizu, Takahiro Okumura, Ryota Morimoto, Shuzo Shimazu, Takashi Yamada, Yuji Kono, Akihiro Hirashiki, Kyosuke Takeshita, Yasuko Kureishi-Bando, Takahisa Kondo, Sumio Yamada, Toyoaki Murohara.
  • Organizer: European Society of Cardiology Congress 2013
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] Abnormality of Nighttime Blood Pressure as a Novel Prognostic Marker in Patients with Dilated Cardiomyopathy. (2013)
  • Author(s): Akinori Sawamura, Takahiro Okumura, Kenji Fukaya, Shinya Shimizu, Ryota Morimoto, Shuzo Shimazu, Akihiro Hirashiki, Kyosuke Takeshita, Yasuko Bando, Toyoaki Murohara.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, USA
• [Book] 救急・集中治療 「心不全－その常識は正しいか－」 (2016)
  • Author(s): 奥村貴裕，加藤真帆人，土肥薫，石原里美，瀬尾由広，佐藤直樹，柴垣有吾，廣谷信一，佐藤幸人，大宮一人，矢川真弓子，橋村一彦，衣笠良治，貞廣威太郎，安村良男，永瀬聡，木田圭亮，大西勝也，絹川弘一郎，大石醒悟
  • Total Pages: 149
  • Publisher: 総合医学社
• [Book] 心不全のすべて (2015)
  • Author(s): 奥村貴裕，今井靖，猪又孝元，波多野将，絹川真太郎，高濱博幸，假屋太郎，牛越博昭，米倉剛，今村輝彦，星出聡，菅野康夫，鈴木健吾，高山守正，江口和男，長山雅俊，中井俊子，絹川弘一郎，塚本泰正，長尾大志，森田啓行
  • Total Pages: 405
  • Publisher: 診断と治療社
• [Book] 最新醫學別冊 新しい診断と治療のABC 心不全 (2015)
  • Author(s): 奥村貴裕，大谷朋仁，加藤真帆人，坂田泰彦，池田善彦，朝野仁裕，中村一文，岸拓弥，佐藤直樹，佐藤幸人，中谷敏，鈴木誠，木田圭亮，猪又孝元，安達仁，溝手勇，簗瀬正伸，大石醒悟，北岡裕章，篠岡太郎
  • Total Pages: 200
  • Publisher: 最新医学社
• [Book] 心不全のすべて (2015)
  • Author(s): 奥村貴裕
  • Total Pages: 300
  • Publisher: 診断と治療社
• [Book] Cardiomyopathies (2013)
  • Author(s): Takahiro Okumura, Toyoaki Murohara.
  • Total Pages: 320
  • Publisher: InTech