The cardiac fibroblast-targeted novel strategy for diastolic heart failure

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590936
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: YOKOYAMA Utako 横浜市立大学, 医学部, 講師 (70404994)
• Co-Investigator(Kenkyū-buntansha): UECHI Masami 横浜市立大学, 医学研究科, 客員教授 (90296426)
• Project Period (FY): 2009 – 2011
• Keywords: 分子心臓病理学 / シグナル伝達

Research Abstract

Activation of the renin-angiotensin-aldosterone system results in vasoconstriction, cardiac hypertrophy and fibrosis. Established arterial stiffness and cardiac dysfunction are key factors contributing to chronic heart failure. Regulation of intracellular concentrations of cyclic AMP is one of the most ubiquitous mechanisms for regulating cellular functions. In this study we showed Epac, an exchange protein activated by cAMP and a new effector molecule of cyclic AMP signaling, inhibited myocardial apoptosis and cardiac dysfunction under activation of aldosterone. Stimulation of Epac may be an alternative strategy for heart failure.

Research Products

• [Journal Article] Inhibition of Phosphodiesterase Type 3 Dilates the Rat Ductus Arteriosus without Inducing Intimal Thickening (2012)
  • Author(s): Ichikawa Y, Yokoyama U, Iwamoto M, Oshikawa J, Okumura S, Sato M, Yokota S, Masuda M, Asou T, Isikawa Y
  • Journal Title: Circ J
  • Peer Reviewed
• [Journal Article] Low-dose Thromboxane A2 Receptor Stimulation Promotes Closure of the Rat Ductus Arteriosus with Minimal Adverse Effects (2012)
  • Author(s): Yokota T, Aida T, Ichikawa Y, Fujita T, Yokoyama U, Minamisawa S
  • Journal Title: Pediatr Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Inhibition of EP4 signaling Attenuates Aortic Aneurysm Formation (2012)
  • Author(s): Yokoyama U, Ishiwata R, Jin MH, Kato Y, Suzuki O, Jin H, Ichikawa Y, Kumagaya S, Katayama Y, Fujita T, Okumura S, Sato M, Sugimoto Y, Aoki H, Suzuki S, Masuda M, Minamisawa S, Ishikawa Y
  • Journal Title: PLoS ONE Volume: (in press)
  • DOI: DOI:10.1371/journal.pone.0036724
  • Peer Reviewed
• [Journal Article] Effect of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia in prostate cancer cells (2012)
  • Author(s): Fukumura H, Sato M, Kezuka K, Sato I, Feng X, Okumura S, Fujita T, Yokoyama U, Eguchi H, Ishikawa Y, Saito T.
  • Journal Title: J Physiol Sci Volume: 62(3) Pages: 251-257
  • DOI: DOI:10.1007/s12576-012-0204-0
  • Peer Reviewed
• [Journal Article] Cyclic AMP and Epac in the regulation of tissue fibrosis (2012)
  • Author(s): Insel PA, Murray F, Yokoyama U, Romano S, Yun H, Brown L, Snead A, Lu D, Aroonsakool N
  • Journal Title: Br. J. Pharmacol Volume: 166(2) Pages: 447-456
  • DOI: DOI:10.1111/j.1476-5381.2012.01847.x
  • Peer Reviewed
• [Journal Article] Secretoglobin 3A2 suppresses bleomycin-induced pulmonary fibrosis by TGFbeta signaling down-regulation (2011)
  • Author(s): Kurotani R, Okumura S, Matsubara T, Yokoyama U, Buckley JR, Tomita T, Kezuka K, Nagano T, Esposito D, Taylor TE, Gillette WK, Ishikawa Y, Abe H, Ward JM, Kimura S
  • Journal Title: J. Biol. Chem Volume: 286(22) Pages: 16982-19692
  • DOI: DOI:10.1074/jbc.M111.239046
  • Peer Reviewed
• [Journal Article] The Roles of Cytochrome P450 in Ischemic Heart Diseas (2011)
  • Author(s): Sato M, Yokoyama U, Fujita T, Okumura S, Ishikawa Y
  • Journal Title: Curr Drug Metab Volume: 12(6) Pages: 526-532
  • URL: http://www.benthamdirect.org/pages/content.php?CDM/2011/00000012/00000006/0002F.SGM
• [Journal Article] Identification of transcription factor E3(TFE3) as a receptor-independent activator of G{alpha} 16 : Gene regulation by nuclear G{alpha} subunit and its activator (2011)
  • Author(s): Sato M, Hiraoka M, Suzuki H, Bai Y, Kurotani R, Yokoyama U, Okumura S, Cismowski MJ, Lanier SM, Ishikawa Y
  • Journal Title: J Biol Chem Volume: 286(20) Pages: 17766-17776
  • DOI: DOI:10.1074/jbc.M111.219816
  • Peer Reviewed
• [Journal Article] DNA microarray profiling identified a new role of growth hormone in vascular remodeling of rat ductus arteriosus (2011)
  • Author(s): Jin MH, Yokoyama U, Sato Y, Shioda A, Jiao Q, Ishikawa Y, Minamisawa S
  • Journal Title: J Physiol Sci Volume: 61(3) Pages: 167-179
  • DOI: DOI:10.1007/s12576-011-0133-3
  • Peer Reviewed
• [Journal Article] Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus (2010)
  • Author(s): Yokoyama U, Minamisawa S, Katayama A, Tang T, Suzuki S, Iwatsubo K, Iwasaki S, Kurotani R, Okumura S, Sato M, Yokota S, Hammond HK, Ishikawa Y
  • Journal Title: Circ Res Volume: 106(12) Pages: 1882-1892
  • DOI: DOI:10.1161/CIRCRESAHA.109.214924
  • Peer Reviewed
• [Journal Article] Differential roles of Epac in regulating cell death in neuronal and myocardial cells (2010)
  • Author(s): Suzuki S, Yokoyama U, Abe T, Kiyonari H, Yamashita N, Kurotani R, Sato M, Okumura S, Ishikawa Y
  • Journal Title: J Biol Chem Volume: 285(31) Pages: 24248-24259
  • DOI: DOI:10.1074/jbc.M109.09458
  • Peer Reviewed
• [Journal Article] Regulation of vascular tone and remodeling of the ductus arteriosus (2010)
  • Author(s): Yokoyama U, Minamisawa S, Ishikawa Y
  • Journal Title: J. Smooth Muscle Res Volume: 46(2) Pages: 77-87
  • DOI: DOI:10.1540/jsmr.46.77
  • Peer Reviewed
• [Journal Article] 運動誘発性発作を呈するQT延長症候群の運動負荷心電図の特徴について (2010)
  • Author(s): 岩本眞理, 西澤崇, 渡部重朗, 市川泰宏, 志水直, 山口和子, 赤池徹, 横山詩子, 瀧聞浄宏, 佐近琢磨, 安井清, 柴田利満, 新村一郎, 横田俊平
  • Journal Title: 日本小児循環器学会雑誌 Volume: 第26巻第1号 Pages: 67-72
  • Peer Reviewed
• [Journal Article] Caveolin gene transfer improves glucose metabolism in diabetic mice (2010)
  • Author(s): Otsu K, Toya Y, Oshikawa J, Kurotani R, Yazawa T, Sato M, Yokoyama U, Umemura S, Minamisawa S, Okumura S, Ishikawa Y
  • Journal Title: Am J Physiol Cell Physiol Volume: 298(3) Pages: C450-456
  • DOI: DOI:10.1152/ajpcell.00077.2009
  • Peer Reviewed
• [Journal Article] T-type Ca2+channels promote oxygenation-induced closure of the rat ductus arteriosus not only by vasoconstriction but also by neointima formation (2009)
  • Author(s): Akaike T, Jin MH, Yokoyama U, Izumi-Nakaseko H, Jiao Q, Iwasaki S, Iwamoto M, Nishimaki S, Sato M, Yokota S, Kamiya Y, Adachi-Akahane S, Ishikawa Y, Minamisawa S
  • Journal Title: J Biol Chem Volume: 284(36) Pages: 24025-24034
  • DOI: DOI:10.1074/jbc.M109.017061
  • Peer Reviewed
• [Presentation] Molecular mechanism of the regulation of vascular elastic fiber formation (2012)
  • Author(s): Yokoyama U, Shioda A, Ishiwata R, Suzuki S, Masuda M, Asou T, Aoki H, Sugimoto Y, Nakamura T, Minamisawa S, Ishikawa Y
  • Organizer: The 89th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 長野県松本文化会館,長野
  • Year and Date: 2012-03-31
• [Presentation] Inhibition of EP4 Signaling Attenuates Mouse Aortic Aneurysm Formation (2012)
  • Author(s): Yokoyama U, Jin MH, Kato Y, Ishiwata R, Suzuki S, Masuda M, Asou T, Aoki H, Sugimoto Y, Nakamura T, Minamisawa S, Ishikawa Y
  • Organizer: The 76rd Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 福岡国際会議場,福岡
  • Year and Date: 2012-03-17
• [Presentation] 動脈管の閉鎖機序と新生児循環管理 (2011)
  • Author(s): 横山詩子
  • Organizer: 第9回日本周産期循環管理研究会
  • Place of Presentation: ハーネル仙台,宮城
  • Year and Date: 2011-11-26
• [Presentation] 動脈管の閉鎖,開存の分子メカニズムと治療開発 (2011)
  • Author(s): 横山詩子
  • Organizer: 横浜市立大学医学部小児科同門会
  • Place of Presentation: ホテルプライム,神奈川
  • Year and Date: 2011-11-10
• [Presentation] 胎生期から始まる血管リモデリングの分子機序 (2011)
  • Author(s): 横山詩子
  • Organizer: 第9回腫瘍病理学分野・探索病理学講座セミナー
  • Place of Presentation: 北海道大学医学部,北海道
  • Year and Date: 2011-09-01
• [Presentation] 臨床から基礎医学研究へ-豊かな感受性を持とう-基礎研究者育成プロジェクト (2011)
  • Author(s): 横山詩子
  • Organizer: 第1回リトリート
  • Place of Presentation: 東京大学医学部,東京
  • Year and Date: 2011-08-20
• [Presentation] 動脈管を制御する分子メカニズム (2011)
  • Author(s): 横山詩子
  • Organizer: 第1回新生児循環基礎・臨床コラボレーションカンファレンスin YOKOHAMA
  • Place of Presentation: 神奈川県立子供医療センター,神奈川
  • Year and Date: 2011-06-22
• [Presentation] 動脈管を制御する分子メカニズム (2011)
  • Author(s): 横山詩子
  • Organizer: 第8回RSVJapan Global Expert Meeting
  • Place of Presentation: 東京国際フォーラム,東京
  • Year and Date: 2011-06-18
• [Presentation] Regulation of vascular remodeling of the ductus arteriosus (2011)
  • Author(s): Yokoyama U, Minamisawa S, Ishikawa Y
  • Organizer: The 88th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: パシフィコ横浜,神奈川
  • Year and Date: 2011-03-29
• [Presentation] Counteracting regulation of vascular remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus (2010)
  • Author(s): Minamisawa S, Yokoyama U, Akaike T, Hammond K, Ishikawa Y
  • Organizer: The 16^<th> International Vascular Biology Meeting
  • Place of Presentation: Los Angeles, USA
  • Year and Date: 20100620-24
• [Presentation] Oxygenation Promotes Migration of Smooth Muscle Cell in the Rat Ductus Arteriosus (2010)
  • Author(s): Minamisawa S, Akaike T, Yokoyama U, Iwasaki S, Ishikawa Y.
  • Organizer: Developmental Vascular Biology Workshop IV
  • Place of Presentation: Monterey, California
  • Year and Date: 20100210-13
• [Presentation] Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus (2010)
  • Author(s): Yokoyama U, Minamisawa S, Katayama A, Tang T, Iwasaki S, Hammond HK, Ishikawa Y.
  • Organizer: Developmental Vascular Biology Workshop IV
  • Place of Presentation: Monterey, California
  • Year and Date: 20100210-13
• [Presentation] 炎症性メディエーターによる血管弾性線維と細胞外基質の制御 (2010)
  • Author(s): 横山詩子
  • Organizer: 大阪大学明石研セミナー
  • Place of Presentation: 大阪大学,大阪
  • Year and Date: 2010-12-07
• [Presentation] Prostaglandin EP4 Signaling Negatively Regulates Vascular Elastic Fiber Assembly (2010)
  • Author(s): Yokoyama U, Shioda A, Kato Y, Asou T, Aoki H, Nakamura T, Minamisawa S, Ishikawa Y
  • Organizer: The 84th Scientific Session, American Heart Association(AHA)
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-16
• [Presentation] 動脈管閉鎖のメカニズム-from bench to bedside (2010)
  • Author(s): 横山詩子
  • Organizer: 第6回横浜小児先端医療セミナー
  • Place of Presentation: 横浜崎陽軒,神奈川
  • Year and Date: 2010-09-03
• [Presentation] 動脈管のリモデリングー酸素の役割 (2010)
  • Author(s): 横山詩子
  • Organizer: 小児心血管分子医学研究会
  • Place of Presentation: シェラトングランデ・トーキョーベイホテル,千葉
  • Year and Date: 2010-07-08
• [Presentation] Prostaglandin E2-activated Epac promotes neointimal formation of the rat ductus arteriosus by a process distinct from that of cAMP-dependent protein kinase A (2010)
  • Author(s): 横山詩子
  • Organizer: 第52回日本平滑筋学会総会栗山煕賞受賞記念講演
  • Place of Presentation: 仙台市情報プラザアエル,宮城
  • Year and Date: 2010-07-01
• [Presentation] Epac1 plays a critical role in advancing vascular remodeling after mechanoinjury in vivo (2010)
  • Author(s): Kato Y, Yokoyama U, Okumura S, Sata M, Minamisawa S, Ishikawa Y
  • Organizer: The 74^<rd> Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 国立京都国際会議場,京都
  • Year and Date: 2010-03-05
• [Remarks]
  • URL: http://www-user.yokohama-cu.ac.jp/～seiri1/index.html