Analysis of relationship between microRNA expression and atrial fibrillation for development of new treatment

• Project/Area Number: 23659668
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: Osaka University
• Principal Investigator: KURATANI Toru 大阪大学, 医学系研究科, 寄附講座教授 (90448035)
• Co-Investigator(Kenkyū-buntansha): SAWA Yoshiki 大阪大学, 大学院・医学系研究科, 教授 (00243220) ; MIYAGAWA Shigeru 大阪大学, 大学院・医学系研究科, 講師 (70544237) ; SHIRAKAWA Yukitoshi 大阪大学, 大学院・医学系研究科, 寄附講座 (20457013) ; NISHI Hiroyuki 大阪大学, 大学院・医学系研究科, 助教 (00529208) ; YOSHIKAWA Yasushi 大阪大学, 大学院・医学系研究科, 助教 (40570594) ; TORIKAI Kei 大阪大学, 大学院・医学系研究科, 助教 (70364792) ; KIN Keiwa 大阪大学, 大学院・医学系研究科, 寄附講座助教 (70532985)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 心房細動 / micro RNA / スタチン

Research Abstract

Although microRNA (miRNA) regulates initiation and/or progression of atrial fibrillation (AF) in canine AF models, the underlying mechanism in humans remains unclear. We speculated that certain miRNAs in atrial tissue are related to AF, and evaluated the relationship of miRNA expression in human atrial tissue in cardiac surgery patients. Right atrial tissues from 29 patients undergoing cardiovascular surgery were divided into 3 groups [A: chronic AF or unsuccessful maze, n=6; B: successful maze, n=10; C: sinus rhythm (SR) n=13]. miRNA microarray analysis showed elevated miRNA-21, miRNA-23b, miRNA-199b, and miRNA-208b in AF as compared to SR groups . RT-PCR showed elevated miRNA-21 (1.9-fold) and miRNA-208b (4.2-fold) in AF as compared to the SR groups. miRNA-21 expression increased from Group C to A (A: 2.1-fold, B: 1.8-fold, C: 1.0-fold). Fibrosis increased from C to A (A: 43.0±12.9%, B: 21.3±6.1%, C: 11.9±3.1%). Percent fibrosis and miRNA-21 expression were correlated (r=0.508, p<0.05). The plasma levels of miRNA-21 in AF patients was significantly decreased as compared to the healthy volunteers (p<0.05).The expression of miRNA-21 in human atrial tissue was found to be related to atrial fibrosis and might affect AF occurrence, indicating its usefulness as a biomarker for cardiac surgery management. We will also conduct the prospective study to clarify the effect of statin on miRNA-21 expression level, and will make experimental animal model to check the efficacy of antagomir.

Research Products

• [Journal Article] Tissue- and plasma-specific microRNA signatures for atherosclerotic abdominal aortic aneurysm. (2012)
  • Author(s): Keiwa Kin
  • Journal Title: Journal of the American Heart Association Volume: e00745 Issue: 5
  • DOI: 10.1161/jaha.112.000745
  • Peer Reviewed
• [Presentation] Department of Cardiovascular SurgeryOsaka University Graduate School of Medicine, Osaka (2011)
  • Author(s): Hiroyuki Nishi; Taichi Sakaguchi; Shigeru Miyagawa; Yasushi Yoshikawa;Satsuki FukushiShunsuke Saito, Takayoshi Ueno, ma, Toru Kuratani, Yoshiki Sawa
  • Organizer: JapanImpact of microRNA expression in human atrial tissue in patients with atrial fibrillation undergoing cardiac surgeryAmerican Heart Association Annual Scientific Session
  • Place of Presentation: Orange County Convention Center. USA
  • Year and Date: 2011-11-15
• [Presentation] Impact of microRNA expression in human atrial tissue in patients with atrial fibrillation undergoing cardiac surger (2011)
  • Author(s): 西 宏之
  • Organizer: American Heart Association Annual Scientific Session
  • Place of Presentation: USA Orlando