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Related Experiment Videos

Somatostatin receptor subtype expression and function in human vascular tissue.

S B Curtis1, J Hewitt, S Yakubovitz

  • 1Department of Surgery, University of British Columbia, Vancouver, Canada.

American Journal of Physiology. Heart and Circulatory Physiology
|June 14, 2000
PubMed
Summary

Angiopeptin failed in human trials because it targets somatostatin receptor 2 (SSTR-2). Human blood vessels primarily use SSTR-1, found in endothelial cells, not SSTR-2, explaining the drug

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Area of Science:

  • Vascular biology
  • Endocrinology
  • Pharmacology

Background:

  • Somatostatin analog angiopeptin inhibits intimal hyperplasia in animal models via somatostatin receptor 2 (SSTR-2).
  • Clinical trials with angiopeptin have yielded disappointing results in humans.
  • Human vascular tissues exhibit differential somatostatin receptor expression compared to animal models.

Purpose of the Study:

  • To investigate the expression profile of somatostatin receptors (SSTRs) in human blood vessels.
  • To determine the specific SSTR subtypes expressed by human endothelial cells.
  • To elucidate the potential reasons for angiopeptin's lack of efficacy in human clinical trials.

Main Methods:

  • Quantitative analysis of SSTR gene expression in human arteries and veins (normal and atherosclerotic).

Related Experiment Videos

  • Immunocytochemistry to localize SSTRs within vascular cell types.
  • In vitro studies on endothelial cell lines (ECV304, HUVEC) to assess SSTR expression and functional responses.
  • Stimulation of endothelial cells with somatostatin and an SSTR-1 specific agonist to observe cytoskeletal changes.

    • Main Results:

    • Human blood vessels predominantly express somatostatin receptor 1 (SSTR-1), with lower levels of SSTR-2 and SSTR-4.
    • SSTR-1 expression was found in endothelial cells but not in vascular smooth muscle cells.
    • Stimulation with somatostatin or an SSTR-1 agonist induced actin cytoskeleton alterations in endothelial cells.
    • No SSTR-3 or SSTR-5 expression was detected in human vascular tissues.

    Conclusions:

    • Human endothelial cells primarily utilize SSTR-1, unlike the SSTR-2 targeted by angiopeptin.
    • Differential expression of SSTR-1 in human vasculature may explain the ineffectiveness of angiopeptin.
    • Targeting SSTR-1 could be a more effective strategy for modulating vascular responses in humans.