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The significance of endothelial cell dysfunction in pulmonary microvessels in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

Research Project

Project/Area Number 17590778
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionYamagata University

Principal Investigator

TAKABATAKE Noriaki  Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (80344795)

Co-Investigator(Kenkyū-buntansha) SHIBATA Yoko  Yamagata University, Faculty of Medicine, Lecturer, 医学部, 講師 (60333978)
TAKEISHI Yasuchika  Yamagata University, Faculty of Medicine, Associate professor, 医学部, 助教授 (40272067)
佐田 誠  山形大学, 医学部, 講師 (00280892)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsCOPD / IPF / Endothelial Injury / 123 I-MIBG肺シンチグラム / 慢性閉塞性肺疾患 / 突発性肺線維症 / 肺毛細血管内皮細胞機能障害
Research Abstract

Prior to investigate the significance of endothelial cell dysfunction in pulmonary micro-vessels in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), we elucidated the association of genetic polymorphisms with acute exacerbations in patients with COPD. Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) are a major cause of morbidity and mortality in COPD. Objectives : The marked heterogeneity in the host defense mechanisms may be attributed to the single nucleotide polymorphisms (SNPs) in the inflammatory chemokine genes that show enhanced expressions in the airway of AECOPD. Methods : We have investigated four SNPs in CCL11, CCL1, and CCL5 genes with relation to the frequency and severity of AECOPD in the retrospective and prospective study of a cohort of 276 male patients with COPD. Measurements and Main Results : In the retrospective study for two years, one SNP (NCBI SNP reference : rs2282691) in the predicted enhancer region o … More f CCL1 gene, encoding a chemotactic factor for a series of leukocytes, including monocytes/macrophages, was significantly associated with the frequency of AECOPD in a dominant model {Fisher's exact test [odds ratio (OR) (95% confidence interval) : 2.70 (1.36-5.36), P=0.004], logistic regression [OR : 3.06 (1.46-6.41), P=0.003], and Kruskal-Wallis test (P=0.003)}. In the prospective study for 30 months, the 'A' allele was a significant risk allele for the severity of AECOPD with obvious gene dosage effect [Kaplan-Meier method with log-rank test ; AA vs. TT ; log-rank statistic : 7.67, P=0.006. Cox proportional hazards regression method ; OR : 5.93 (1.28-27.48), P=0.023]. The electromobility shift assay showed that C/EBPβ, a key transcriptional factor in response to pulmonary infections, binds to the 'T' allele, but not to the 'A' allele. Conclusions : Variants in CCL1 gene are associated with susceptibility to AECOPD through their potential implication in the heterogeneous features of the host defense mechanisms against AECOPD. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (5 results)

All 2006 2005

All Journal Article (5 results)

  • [Journal Article] A single nucleotide polymorphism in the CCL1 gene predicts acute exacerbations in chronic obstructive pulmonary disease2006

    • Author(s)
      Takabatake N. et al.
    • Journal Title

      Am J Respir Crit Care Med. 174

      Pages: 875-885

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A single nucleotide polymorphism in the CCL1 gene predicts acute exacerbations in chronic obstructive pulmonary disease.2006

    • Author(s)
      Takabatake N. et al.
    • Journal Title

      Am J Respir Crit Care Med 174

      Pages: 875-885

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A single nucleotide polymorphism in the CCL1 gene predicts acute exacerbations in chronic obstructive pulmonary disease.2006

    • Author(s)
      Takabatake N. et al.
    • Journal Title

      Am J Respir Crit Care Med. 174

      Pages: 875-885

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Circulating levels of soluble Fas ligand in cachexic patients with COPD are higher than those in non-cachexic patients with COPD2005

    • Author(s)
      Takabatake N.et al.
    • Journal Title

      Intern Med. 44

      Pages: 1137-1143

    • NAID

      10016885943

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Impaired systemic cell-mediated immunity and increased susceptibility to acute respiratorv tract infections in patients with COPD.2005

    • Author(s)
      Takabatake N.et al.
    • Journal Title

      Respir Med 99

      Pages: 485-492

    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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