急性肺障害における血管内皮前駆細胞の動態解析:自家移植による再生治療の試み

• Project/Area Number: 21592318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Fujita Health University (2010-2011); Aichi Medical University (2009)
• Principal Investigator: TAKEYAMA Naoshi 藤田保健衛生大学, 医学部, 教授 (00155053)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 集中治療 / ALI/ARDS / 急性肺障害 / 内皮前駆細胞 / 自家移植 / VEGF / CD133 / CD31 / CD34 / syto16 / FACS / 血管内皮前駆細胞

Research Abstract

Objective : Impaired fibrinolysis is associated with a higher incidence of both multiple organ dysfunction and mortality in the intensive care unit(ICU). Plasminogen activator inhibitor(PAI)-1 is the chief inhibitor of fibrinolysis. We investigated the influence of the 4G/5G polymorphism(rs1799768) of the PAI-1 gene on the plasma PAI-1 level and the outcome of critically ill patients. Methods : In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism was assessed, plasma PAI-1 and arterial lactate concentrations were measured and clinical severity scores were recorded. Results : Homozygotes for the 4G allele had higher plasma levels of PAI-1 antigen. The mean 8 SD PAI-1 antigen level was 193.318 167.93 ng/ml for the 4G/4G genotype, 100.67 8 114.16 ng/ml for the 4G/5G genotype and 0.43 8 0.53 ng/ml for the 5G/5G genotype. There was a significant correlation between plasma PAI-1 and arterial lactate concentrations, as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and 0% for patients with the 4G/4G, 4G/5G and 5G/5G genotypes, respectively. Conclusions : These results demonstrate that the 4G/5G polymorphism of the PAI-1 gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and cause organ failure, and thus the presence of the 4G allele increases the risk of death.

Research Products

• [Journal Article] 4G/5G polymorphism of the plasminogen activator-1 gene is associated with multiple organ dysfunction in critically ill patients (2012)
  • Author(s): Huq MA, Takeyama N, Harada M, Miki Y, Takeuchi A, Inoue S, Nakagawa T, Kanou H, Hirakawa A, Noguchi H
  • Journal Title: Acta Haematologica Volume: 127 Pages: 72-80
  • Peer Reviewed
• [Journal Article] 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients (2012)
  • Author(s): Huq MA, Takeyama N, Harada M, Miki Y
  • Journal Title: Acta Haematologica Volume: 127 Pages: 72-80
  • Peer Reviewed
• [Presentation] 4G/5G polymorphism of the PAI-1 gene is associated with multiple organ dysfunction in ICU patients (2012)
  • Author(s): Huq A, Takeyama N, Hirakawa A
  • Organizer: The 12^<th> Joint Scientific Congress of JAICM and KSCCM
  • Place of Presentation: 千葉
  • Year and Date: 2012-02-29
• [Presentation] 4G/5G polymorphism of the PAI-1 gene is associated with multiple organ dysfunction in ICU patients (2012)
  • Author(s): Huq MA, Takeyama N, Hirakawa A, et al
  • Organizer: The 12th joint scientific congress of KSCCM and JSICM
  • Place of Presentation: Chiba