Development of Chronotherapy for Cardiovascular Diseases

• Project/Area Number: 21390244
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Nagasaki University
• Principal Investigator: MAEMURA Koji 長崎大学, 大学院・医歯薬学総合研究科, 教授 (90282649)
• Co-Investigator(Kenkyū-buntansha): IKEDA Satoshi 長崎大学, 大学院・医歯薬学総合研究科, 講師 (10336159)
• Co-Investigator(Renkei-kenkyūsha): MORITA Hiroyuki 東京大学, 大学院・医学系研究科, 特任准教授 (60323573) ; SADANAGA Tsuneaki 熊本市立植木病院
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 循環器疾患 / 時間薬理学 / メラトニン / 時間医学 / 血管内皮機能

Research Abstract

We investigated the effect of administration time of RAS blockades on renal function associated with congestive heart failure. The patients who took RAS blockades in the evening showed less urinary albumin excretion compared with those in the morning. Melatonin, which exhibits clear circadian rhythm, suppressed ROS generation in endothelial cells and improved endothelial function. The results define the potential clinical applicability of melatonin to the prevention from cardiovascular diseases, especially in patients who are under disturbed circadian rhythm.

Research Products

• [Journal Article] Rivaroxaban in patients with a recent acute coronary syndrome (2012)
  • Author(s): Mega JL, Braunwald E, Wiviott SD, Basssand JR, Bhatt DL, Bode C, Burton P, Cohen M, Cook-Bruns N, Fox KA, Goto S, Murphy SA, Plotnikov AN, Schneider D, Sun X, Verheugt FW, Gibson CM; ATLAS ACS 2-TIMI 51 Investigators
  • Journal Title: N Engl J Med Volume: 366 Issue: 1 Pages: 9-19
  • DOI: 10.1056/nejmoa1112277
  • Peer Reviewed
• [Journal Article] Low glomerular filtration rate is associated with high prevalence of vasospastic angina (2011)
  • Author(s): Koga S, Ikeda S, Nakata T, Yasunaga T, Takeno M, Koide Y, Maemura K.
  • Journal Title: Circ J Volume: 75 Pages: 1691-1695
  • NAID: 10029126777
  • Peer Reviewed
• [Journal Article] Incidence and prognostic value of early repolarization pattern in the 12-lead electrocardiogram (2011)
  • Author(s): Haruta D, Matsuo K, Tsuneto A, Ichimaru S, Hida A, Sera N, Imaizumi M, Nakashima E, Maemura K, Akahoshi M.
  • Journal Title: Circulation Volume: 123 Pages: 2931-2937
  • Peer Reviewed
• [Journal Article] Circadian clock and cardiovascular disease (2011)
  • Author(s): Takeda N, Maemura K.
  • Journal Title: J Cardiol Volume: 57 Pages: 249-256
• [Journal Article] Ezetimibe and vascular endothelial function (2011)
  • Author(s): Ikeda S, Maemura K.
  • Journal Title: Curr Vasc Pharmacol Volume: 9 Pages: 87-98
  • NAID: 120006985261
  • Peer Reviewed
• [Journal Article] メタボリックシンドロームと概日リズム.メタボリックシンドロームII(後篇)-メタボリックシンドロームの基礎- (2011)
  • Author(s): 前村浩二
  • Journal Title: 最新医学 Volume: 66(6月増刊) Pages: 1477-86
• [Journal Article] 生体リズムの乱れを調整する3要素(光、食事、メラトニン) (2011)
  • Author(s): 前村浩二
  • Journal Title: 心臓 Volume: 43(2) Pages: 154-158
  • NAID: 130002146637
• [Journal Article] Negatively charged low-density lipoprotein is associated with atherogenic risk in hypertensive patients (2011)
  • Author(s): Urata J, Ikeda S, Koga S, Nakata T, Yasunaga T, Sonoda K, Koide Y, Ashizawa N, Kohno S, Maemura K
  • Journal Title: Heart Vessels Volume: Epub Apr 14 Issue: 3 Pages: 235-242
  • DOI: 10.1007/s00380-011-0139-z
  • NAID: 120006985130
  • Peer Reviewed
• [Journal Article] Apixaban versus warfarin in patients with atrial fibrillation (2011)
  • Author(s): Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators
  • Journal Title: N Engl J Med Volume: 365 Issue: 11 Pages: 981-992
  • DOI: 10.1056/nejmoa1107039
  • Peer Reviewed
• [Journal Article] Determinants of Warfarin Use and International Normalized Ratio Levels in Atrial Fibrillation Patients in Japan - Subanalysis of the J-RHYTHM Registry - (2011)
  • Author(s): J-RHYTHM Registry Investigators
  • Journal Title: Circulation Journal Volume: 75 Issue: 10 Pages: 2357-2362
  • DOI: 10.1253/circj.CJ-11-0427
  • NAID: 10029459312
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Present Status of Anticoagulation Treatment in Japanese Patients With Atrial Fibrillation - A Report From the J-RHYTHM Registry - (2011)
  • Author(s): Atarashi H, Inoue H, Okumura K, Yamashita T, Kumagai N, Origasa H; J-RHYTHM Registry Investigators
  • Journal Title: Circulation Journal Volume: 75 Issue: 6 Pages: 1328-1333
  • DOI: 10.1253/circj.CJ-10-1119
  • NAID: 10028148514
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension : a randomized controlled trial (2011)
  • Author(s): Matsuzaki M, Ogihara T, Umemoto S, Rakugi H, Matsuoka H, Shimada K, Abe K, Suzuki N, Eto T, Higaki J, Ito S, Kamiya A, Kikuchi K, Suzuki H, Tei C, Ohashi Y, Saruta T; Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial Group
  • Journal Title: J Hypertens Volume: 29 Issue: 8 Pages: 1649-1659
  • DOI: 10.1097/hjh.0b013e328348345d
  • Peer Reviewed
• [Journal Article] Graves' disease complicated by ventricular fibrillation in three men who were smokers (2011)
  • Author(s): Ando T, Henmi T, Haruta D, Haraguchi A, Ueki I, Horie I, Imaizumi M, Usa T, Maemura K, Kawakami A
  • Journal Title: Thyroid Volume: 21 Issue: 9 Pages: 1021-1025
  • DOI: 10.1089/thy.2010.0368
  • NAID: 120006984991
  • Peer Reviewed
• [Journal Article] Low Glomerular Filtration Rate Is Associated With High Prevalence of Vasospastic Angina (2011)
  • Author(s): Koga S, Ikeda S, Nakata T, Yasunaga T, Takeno M, Koide Y, Maemura K
  • Journal Title: Circulation Journal Volume: 75 Issue: 7 Pages: 1691-1695
  • DOI: 10.1253/circj.CJ-10-0864
  • NAID: 10029126777
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated with Early Repolarization (2011)
  • Author(s): Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Makiyama T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M, Aizawa Y, Shimizu W, Makita N
  • Journal Title: Circ Arrhythm Electrophysiol Volume: 4 Issue: 6 Pages: 874-881
  • DOI: 10.1161/circep.111.963983
  • Peer Reviewed
• [Journal Article] 概日リズムを考慮した生活習慣病の診療 (2011)
  • Author(s): 前村浩二
  • Journal Title: 呼吸と循環 Volume: 59 Pages: 223-223
• [Journal Article] メタボリックシンドロームと概日リズム (2011)
  • Author(s): 前村浩二
  • Journal Title: 最新医学 Volume: 66 Pages: 1477-1486
• [Journal Article] PTX3による心血管疾患の診断 (2011)
  • Author(s): 前村浩二
  • Journal Title: 循環器内科 Volume: 69 Pages: 613-618
  • NAID: 40018927322
• [Journal Article] 動脈硬化の新展開-イベントを起こす前に-循環器疾患における体内時計の意義 (2011)
  • Author(s): 前村浩二
  • Journal Title: 進歩する心臓研究-Tokyo Heart Journal- Volume: 31 Pages: 28-34
• [Journal Article] Increased Akt-mTOR Signaling in Lung Epithelium Is Associated with Respiratory Distress Syndrome in Mice (2011)
  • Author(s): Ikeda, H., Shiojima, I., Oka, T.Yoshida, M., Maemura, K.Walsh, K., Igarashi, T., Komuro, I.
  • Journal Title: Mol Cell Biol Volume: 31 Pages: 1054-65
  • Peer Reviewed
• [Journal Article] Cardiovascular disease, chronopharmacotherapy, and the molecular clock (2010)
  • Author(s): Takeda N, Maemura K.
  • Journal Title: Adv Drug Deliv Rev Volume: 62 Pages: 956-66
  • Peer Reviewed
• [Journal Article] Circadian clock and vascular disease (2010)
  • Author(s): Takeda N, Maemura K.
  • Journal Title: Hypertens Res Volume: 33 Pages: 645-651
  • NAID: 10026519888
  • Peer Reviewed
• [Journal Article] A critical role of sympathetic nerve regulation for the treatment of impaired daily rhythm in hypertensive Dahl rats (2010)
  • Author(s): Suzuki J, Ogawa M, Tamura N, Maejima Y, Takayama K, Maemura K, Honda K, Hirata Y, Nagai R, Isobe M.
  • Journal Title: Hypertens Res Volume: 33 Pages: 1060-1065
  • NAID: 10027475456
  • Peer Reviewed
• [Journal Article] 循環器領域における時間生物学 (2010)
  • Author(s): 前村浩二
  • Journal Title: 日本心電学会誌心電図JPN JElectrocardiology 30 supple Volume: 3 Pages: 43-52
• [Journal Article] A critical role of sympathetic nerve regulation for the treatment of impaired daily rhythm in hypertensive Dahl rats (2010)
  • Author(s): Suzuki, J., Ogawa, M., Tamura, N., Maejima, Y., Takayama, K.Maemura, K., Honda, K., Hirata, Y., Nagai, R., Isobe, M.
  • Journal Title: Hypertens Res Volume: 33 Pages: 1060-65
  • NAID: 10027475456
  • Peer Reviewed
• [Journal Article] Circadian clock and vascular disease (2010)
  • Author(s): Takeda, N., Maemura, K.
  • Journal Title: Hypertens Res Volume: 33 Pages: 645-51
  • NAID: 10026519888
  • Peer Reviewed
• [Journal Article] Fatty liver incidence and predictive variables (2010)
  • Author(s): Tsuneto, A., Hida, A., Sera, N.Imaizumi, M., Ichimaru, S., Nakashima, E., Seto, S.Maemura, K., Akahoshi, M.
  • Journal Title: Hypertens Res Volume: 33 Pages: 638-43
  • NAID: 10026397413
  • Peer Reviewed
• [Journal Article] 循環器領域における時間生物学 (2010)
  • Author(s): 前村浩二
  • Journal Title: Jpn J Electrocardiology Volume: 40 Pages: 43-52
  • Peer Reviewed
• [Journal Article] 生体リズム研究の最近の進歩:心血管系を調節する時計機構 時計機構に連関するHIF遺伝子の役割 (2010)
  • Author(s): 武田憲彦、前村浩二
  • Journal Title: 日本抗加齢医学会雑誌アンチ・エイジング医学 Volume: 68 Pages: 482-8
• [Journal Article] アンチエイジングのバイオロジー 老化と時計遺伝子 (2010)
  • Author(s): 武田憲彦、前村浩二
  • Journal Title: 循環器内科 Volume: 6 Pages: 84-8
• [Journal Article] Role of endostatin in cardiovascular remodeling (2010)
  • Author(s): Maemura K
  • Journal Title: Circ J. 74 Pages: 45-46
  • NAID: 10025941101
  • Peer Reviewed
• [Journal Article] Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcifica tion. (2010)
  • Author(s): Son BK, Akishita M, Iijima K, Ogawa S, Maemura K, Yu J, Takeyama K, Kato S, Eto M, Ouchi Y.
  • Journal Title: J Biol Chem. 285 Pages: 7537-7544
  • Peer Reviewed
• [Journal Article] 循環器領域の時間治療 (2009)
  • Author(s): 前村浩二
  • Journal Title: 心臓 Volume: 41(10) Pages: 1067-1067
  • NAID: 130003376800
• [Journal Article] 特集ストレス・日内変動と循環器疾患.エビデンスとその発生機序-循環器疾患と時計遺伝子 (2009)
  • Author(s): 前村浩二
  • Journal Title: 循環器科 Volume: 66(2) Pages: 202-208
• [Journal Article] 特集時間薬理学～最適な投与方法を求め～循環器疾患の時間治療 (2009)
  • Author(s): 前村浩二
  • Journal Title: 医薬ジャーナル Volume: 45(69) Pages: 137-141
• [Journal Article] 特集:生体リズムから心血管病を探る血管内皮と時計遺伝子の関連性をみる (2009)
  • Author(s): 前村浩二
  • Journal Title: Vascular Medicine Volume: 5(4) Pages: 43-49
• [Journal Article] 特集時間と病気生体時計から時間医学へ循環器疾患のリズム (2009)
  • Author(s): 前村浩二
  • Journal Title: Medical Bio Volume: 11 Pages: 42-46
• [Journal Article] Images in cardiovascular medicine. Lung perfusion blood volume computed tomographic images of pulmonary embolism : before and after thrombolysis (2009)
  • Author(s): Sueyoshi E, Tsutsui S, Sakamo to I, Uetani M, Maemura K.
  • Journal Title: Circulation 119 Pages: 3242-3243
  • Peer Reviewed
• [Journal Article] SLCO4C1 transporter eliminates uremic toxins and attenuates hyperten sion and renal inflammation. (2009)
  • Author(s): Toyohara T, Suzuki T, Morimoto R, Akiyama Y, Souma T, Shiwaku HO, Takeuchi Y, Mishima E, Abe M, Tanemoto M, Masuda S, Kawano H, Maemura K, Nakayama M, Sato H, Mikkaichi T, Yamaguchi H, Fukui S, Fukumoto Y, Shimokawa H, Inui K, Terasaki T, Goto J, Ito S, Hishinuma T, Rubera I, Tauc M, Fujii-Kuriyama Y, Yabuuchi H, Moriyama Y, Soga T, Abe T.
  • Journal Title: J Am Soc Nephrol. 20 Pages: 2546-2555
  • Peer Reviewed
• [Journal Article] Kruppel-like Factor 2 Inhibits Hypoxia-inducible Factor 1α Expression and Function in the Endothelium. (2009)
  • Author(s): Kawanami D, Mahabeleshwar GH, Lin Z, Atkins GB, Hamik A, Haldar SM, Maemura K, Lamanna JC, Jain MK.
  • Journal Title: J Biol Chem. 20 Pages: 2545-2555
  • Peer Reviewed
• [Journal Article] 時間薬理学～最適な投与方法を求めて～ 循環器疾患の時間治療 (2009)
  • Author(s): 前村浩二
  • Journal Title: 医薬ジャーナル 284 Pages: 20522-20530
• [Journal Article] 時間と病気 生体時計から時間医学へ 循環器疾患のリズム (2009)
  • Author(s): 前村浩二
  • Journal Title: Medical Bio 11 Pages: 42-46
• [Journal Article] 特集 : 生体リズムから心血管病を探る 血管内皮と時計遺伝子の関連性をみる (2009)
  • Author(s): 前村浩二
  • Journal Title: Vascular Medicine 5 Pages: 43-49
• [Journal Article] サーカディアンリズムを考慮した心血管イベント発症抑制 (2009)
  • Author(s): 藤田敏郎、前村浩二
  • Journal Title: Pharma Medica 27 Pages: 153-156
• [Journal Article] 特集 ストレス・日内変動と循環器疾患-エビデンスとその発生機序- 循環器疾患と時計遺伝子 (2009)
  • Author(s): 前村浩二
  • Journal Title: 循環器科 66 Pages: 202-208
• [Journal Article] 動脈硬化治療の最前線 巻頭言 (2009)
  • Author(s): 前村浩二
  • Journal Title: Medical View Point 30 Pages: 1-1
• [Journal Article] 心血管病の診断と治療におけるバイオマーカーの有用性 PTX3 (2009)
  • Author(s): 志賀太郎、前村浩二
  • Journal Title: Mebio 26 Pages: 42-49
• [Journal Article] 循環器領域の時間治療 (2009)
  • Author(s): 前村浩二
  • Journal Title: 心臓 41 Pages: 1067-1067
  • NAID: 130003376800
• [Journal Article] 血圧日内変動と臓器障害 (2009)
  • Author(s): 木村玄次郎、長谷部直幸、苅尾七臣、前村浩二
  • Journal Title: 血圧 16 Pages: 65-70
• [Presentation] Circadian Clock and Cardiovascular Diseases-Overview (2012)
  • Author(s): 前村浩二
  • Organizer: 第76回日本循環器学会年次学術集会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2012-03-17
• [Presentation] Circadian Clock and Cardiovascular Diseases-Overview (2012)
  • Author(s): 前村浩二
  • Organizer: 第76回日本循環器学会年次学術集会トピックス:体内時計と循環器疾患
  • Place of Presentation: 福岡
• [Presentation] 生活習慣病発症における体内時計の意義 (2011)
  • Author(s): 前村浩二
  • Organizer: 第18回日本時間生物学会学術大会
  • Place of Presentation: 名古屋大学(愛知県)
  • Year and Date: 2011-11-25
• [Presentation] 循環器疾患発症における生物時計の意義 (2011)
  • Author(s): 前村浩二
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2011-09-22
• [Presentation] Role of Clock Genes in the Development of Cardiovascular Disease (2011)
  • Author(s): 前村浩二
  • Organizer: 第75回日本循環器学会年次学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-08-03
• [Presentation] 生活習慣病発症における体内時計の意義 (2011)
  • Author(s): 前村浩二
  • Organizer: 第18回日本時間生物学会学術大会シンポジウム:臨床時間生物学の現状と展望
  • Place of Presentation: 名古屋
• [Presentation] 循環器疾患発症における生物時計の意義 (2011)
  • Author(s): 前村浩二
  • Organizer: 第84回日本生化学会大会シンポジウム:生物時計と代謝制御.中枢時計から末梢時計へ
  • Place of Presentation: 京都
• [Presentation] Role of Clock Genes in the Development of Cardiovascular Disease (2011)
  • Author(s): 前村浩二
  • Organizer: 第75回日本循環器学会年次学術集会Focus Session : Cardio-Metabolic" Clock" and" Memory"
  • Place of Presentation: 横浜
• [Presentation] 体内時計と心血管疾患 (2011)
  • Author(s): 前村浩二
  • Organizer: 第28回日本医学会総会東日本大震災のためWeb上での開催)教育講演:循環と呼吸
  • Place of Presentation: 東京
• [Presentation] 体内時計と心血管疾患 (2011)
  • Author(s): 前村浩二
  • Organizer: 第28回日本医学会総会
  • Place of Presentation: (震災のためWeb開催)
• [Presentation] The Role of Biological Clock in Cardiovascular Diseases (2010)
  • Author(s): Koji Maemura
  • Organizer: 第18回日本血管生物医学会学術大会シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-01
• [Presentation] The Role of Biological Clock in Cardiovascular Diseases (2010)
  • Author(s): Koji Maemura
  • Organizer: 第18回 日本血管生物医学会学術大会
  • Place of Presentation: 梅田スカイビル(大阪府)(招待講演)
  • Year and Date: 2010-12-01
• [Presentation] 循環器診療におけるバイオマーカーの使い方 (2010)
  • Author(s): 前村浩二
  • Organizer: 第397回長崎医学会例会
  • Place of Presentation: 長崎インターナショナルホテル(長崎県)(招待講演)
  • Year and Date: 2010-07-28
• [Presentation] 生体リズムと時間医学 (2010)
  • Author(s): 前村浩二
  • Organizer: 第14回日本適応医学会学術集会
  • Place of Presentation: 日本学術総合センター(東京都)(招待講演)
  • Year and Date: 2010-07-03
• [Presentation] The Role of long Pentraxin3 in Cardiovascular Diseases (2010)
  • Author(s): Koji Maemura
  • Organizer: XX World Congress ISHR
  • Place of Presentation: 京都国際会議場(京都府)(招待講演)
  • Year and Date: 2010-05-14
• [Presentation] Keynote Lecture : Application of Endothelial Cell Biomarker to Cardiovascular Disease Prevention and Treatment (2010)
  • Author(s): 前村浩二
  • Organizer: 第74回日本循環器学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-07
• [Presentation] 循環器疾患におけるサーカディアンリズムの意義 (2009)
  • Author(s): 前村浩二
  • Organizer: 第13回日本心不全学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-10-31
• [Presentation] 循環器疾患とサーカディアンリズム (2009)
  • Author(s): 前村浩二
  • Organizer: 第19回日本医療薬学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2009-10-25
• [Presentation] 教育講演 循環器疾患とサーカディアンリズム (2009)
  • Author(s): 前村浩二
  • Organizer: 第19回日本医療薬学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2009-10-25
• [Presentation] 招請講演 血管内皮機能と循環器疾患 (2009)
  • Author(s): 前村浩二
  • Organizer: 九州麻酔科学会第47回大会
  • Place of Presentation: 長崎
  • Year and Date: 2009-10-10
• [Book] 概日リズム (2011)
  • Author(s): 前村浩二
  • Publisher: 朝倉書店,東京
• [Book] 生活習慣病の薬物療法 (2011)
  • Author(s): 前村浩二
  • Publisher: 日本評論社,東京
• [Book] Novel Molecular and Cellular Therapeutic Advances for Heart Disease AHA Highlights 2009 (2010)
  • Author(s): 前村浩二
  • Total Pages: 154
  • Publisher: 協和企画
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/junkanki/research/index.html
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/junkanki/index.html
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/junkanki/index.html