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Related Experiment Videos

Augmented urokinase receptor expression in atheroma

H Noda-Heiny1, A Daugherty, B E Sobel

  • 1Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|January 1, 1995
PubMed
Summary

Increased expression of urokinase plasminogen activator receptor (uPA-R) on vascular smooth muscle cells in atheroma promotes cell migration and neointimalization, contributing to atherosclerosis development.

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Area of Science:

  • Cardiovascular Biology
  • Cell Biology
  • Atherosclerosis Research

Background:

  • Smooth muscle cell proliferation and migration are key processes in atherosclerosis.
  • The role of plasminogen activators and their receptors in atherogenesis is not fully understood.
  • The receptor for urokinase-type plasminogen activator (uPA-R) is a potential mediator of these cellular events.

Purpose of the Study:

  • To investigate the expression and localization of uPA-R in atherosclerotic lesions.
  • To determine the role of uPA-R in vascular smooth muscle cell migration in atheroma.

Main Methods:

  • Immunostaining of atherosclerotic lesions from rabbits and humans to detect uPA-R.
  • Western blotting to quantify uPA-R protein levels in normal and diseased vessels.

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  • In vitro studies using cultured vascular smooth muscle cells and antibodies to uPA-R.
  • Main Results:

    • uPA-R was highly expressed in the neointima of atherosclerotic lesions but not in normal arteries.
    • uPA-R was localized to macrophages and smooth muscle cells within the neointima.
    • uPA-R protein levels were significantly higher in atheroma compared to normal vessels.
    • Antibodies targeting uPA-R inhibited vascular smooth muscle cell migration in vitro.
    • uPA-R mRNA levels did not significantly increase in migrating cells, suggesting posttranscriptional regulation.

    Conclusions:

    • Increased cell-surface uPA-R in atheroma contributes to pericellular proteolysis.
    • Elevated uPA-R promotes vascular smooth muscle cell migration, leading to neointimalization in atherosclerosis.
    • Altered posttranscriptional regulation may be responsible for increased uPA-R levels in atheroma.