Experimental study on calcium signaling in coronary spastic angina animal model

• Project/Area Number: 25860577
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Hirosaki University
• Principal Investigator: Yokota Takashi 弘前大学, 医学部附属病院, 助教 (40624888)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 冠攣縮 / カルシウム / カルシウム拮抗薬

Outline of Final Research Achievements

We recently showed that coronary spasm is induced in transgenic mice with enhanced phospholipase C-delta 1 activity (PLC-TG). Although calcium antagonist therapy is established as a treatment for coronary spastic angina, its precise mechanism remains unclear. In the present study, we investigated the efficacy of calcium antagonist and its mechanism using the PLC-TG mice. Calcium antagonist suppressed coronary spasm in the PLC-TG mice, as in the clinical cases. Alterations in protein expression levels and activity of calcium channels were suggested to be implicated in the pathogenesis of coronary spasm and in the therapeutic effect of calcium antagonist. Our study may help better understand calcium signaling in the coronary spasm and contribute to the development of novel therapy for drug-resistant coronary spasm.

Research Products

• [Journal Article] Coronary Calcification and Plaque Vulnerability: An Optical Coherence Tomographic Study (2016)
  • Author(s): Ong DS, Lee JS, Soeda T, Higuma T, Minami Y, Wang Z, Lee H, Yokoyama H, Yokota T, Okumura K, Jang IK
  • Journal Title: Circ Cardiovasc Imaging Volume: 9 Issue: 1
  • DOI: 10.1161/circimaging.115.003929
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enhanced p122RhoGAP/DLC-1 expression can be a cause of coronary spasm. (2015)
  • Author(s): Kinjo T, Tanaka M, Osanai T, Shibutani S, Narita I, Tanno T, Nishizaki K, Ichikawa H, Kimura Y, Ishida Y, Yokota T, Shimada M, Homma Y, Tomita H, Okumura K.
  • Journal Title: PLOS ONE Volume: 10(12) Issue: 12 Pages: e0143884-e0143884
  • DOI: 10.1371/journal.pone.0143884
  • Peer Reviewed / Open Access
• [Journal Article] Imidapril and enalapril similarly inhibit plasma matrix metalloproteinase activities and attenuate left ventricular remodeling in patients with acute myocardial infarction (2014)
  • Author(s): Yokota T, Tomita H, Mori Y, Kudo T, Hiraga H, Suto N, Higuma T, Abe N, Hanada H, Osanai T, Okumura K.
  • Journal Title: J Cardiovasc Pharmacol Volume: 63 Issue: 6 Pages: 528-532
  • DOI: 10.1097/fjc.0000000000000077
  • Peer Reviewed
• [Journal Article] Low serum eicosapentaenoic acid level is a risk for ventricular arrhythmia in patients with acute myocardial infarction: a possible link to J-waves (2014)
  • Author(s): Endo T, Tomita H, Higuma T, Abe N, Kushibiki M, Saitoh S, Yamada M, Yokota T, Echizen T, Yokoyama H, Tateyama S, Suzuki A, Ishida Y, Murakami K, Osanai T, Okumura K.
  • Journal Title: Heart Vessels Volume: 29 Issue: 6 Pages: 847-854
  • DOI: 10.1007/s00380-013-0435-x
  • Peer Reviewed
• [Presentation] Prasugrel Versus Clopidogrel for Residual Thrombus Burden: An Optical Coherence Tomography Study (2016)
  • Author(s): 横田 貴志、樋熊拓未、西崎史恵、泉山圭、横山公章、山田雅大、富田泰史、奥村謙
  • Organizer: The 80th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 仙台国際センター（宮城県、仙台市）
  • Year and Date: 2016-03-18
• [Presentation] ステント留置術後の円錐枝の閉塞によりBrugada症候群様の心電図変化を示し、その後心室細動を来した1症例 (2015)
  • Author(s): 横田 貴志、加藤 朋、對馬 迪子、西崎 史恵、泉山 圭、横山 公章、山田 雅大、富田 泰史、樋熊 拓未、奥村 謙
  • Organizer: 第38回日本心血管インターベンション治療学会 東北地方会
  • Place of Presentation: 公益ホール（山形県、酒田市）
  • Year and Date: 2015-07-25