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Plasminogen activator inhibitor-1 is a major stress-regulated gene: Implications for stress-induced thrombosis in aged individuals

Academic Article
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Overview

authors

  • Yamamoto, K.
  • Takeshita, K.
  • Shimokawa, T.
  • Yi, H.
  • Isobe, K.
  • Loskutoff, David J.
  • Saito, H.

publication date

  • January 2002

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Plasminogen activator inhibitor-1 (PAI-1) is one of the primary inhibitors of the fibrinolytic system and has been implicated in a variety of thrombotic disorders. In this report, stress-induced changes in murine PAI-1 gene expression were investigated to study the role of this inhibitor in the development of stress-induced hypercoagulability. Restraint stress led to a dramatic induction of plasma PAI-1 antigen and of tissue PAI-1 mRNA with maximum induction in adipose tissues. In situ hybridization analysis of the stressed mice revealed that strong signals for PAI-1 mRNA were localized to hepatocytes, renal tubular epithelial cells, adrenomedullar chromaffin cells, neural cells in the paraaortic sympathetic ganglion, vascular smooth muscle cells, and adipocytes, but not to endothelial cells. These observations indicate that the stress induces the PAI-1 gene expression in a tissue-specific and cell type-specific manner. The induction of PAI-1 mRNA by restraint stress was greater than that observed for heat shock protein, a typical stress protein, suggesting that PAI-1 is one of the most highly induced stress proteins. Importantly, the magnitude of induction of PAI-1 mRNA by stress increased markedly with age, and this increase in PAI-1 correlated with tissue thrombosis in the older stressed mice. Moreover, much less tissue thrombosis was induced by restraint stress in young and aged PAI-1-deficient mice compared with age-matched wild-type mice. These results suggest that the large induction of PAI-1 by stress increases the risk for thrombosis in the older populations, and that the adipose tissue may be involved.

subject areas

  • Aging
  • Animals
  • Female
  • Gene Expression
  • HSP70 Heat-Shock Proteins
  • In Situ Hybridization
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasminogen Activator Inhibitor 1
  • Protozoan Proteins
  • RNA, Messenger
  • Restraint, Physical
  • Stress, Physiological
  • Thrombosis
  • Tissue Distribution
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Identity

PubMed Central ID

  • PMC117401

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.022608799

PubMed ID

  • 11792849
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Additional Document Info

start page

  • 890

end page

  • 895

volume

  • 99

issue

  • 2

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