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Endothelins are angiogenic.

E L Bek1, M A McMillen

  • 1Department of Surgery, Michael Reese Hospital and Medical Center and the University of Illinois at Chicago, College of Medicine, USA. eugenebek@aol.com

Journal of Cardiovascular Pharmacology
|November 15, 2000
PubMed
Summary
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Endothelins-1 and -3 (ET-1, ET-3) promote new blood vessel growth (angiogenesis) in rat corneas. This direct effect is mediated by the ET(A) receptor and is not dependent on leukocytes.

Area of Science:

  • Ophthalmology
  • Vascular Biology
  • Endocrinology

Background:

  • Endothelins (ETs) are potent vasoactive peptides.
  • Their role in angiogenesis, particularly in ocular tissues, requires further elucidation.
  • Understanding ET-mediated angiogenesis is crucial for developing therapies for angiogenesis-related eye diseases.

Purpose of the Study:

  • To investigate the angiogenic potential of Endothelin-1 (ET-1) and Endothelin-3 (ET-3) in a rat cornea model.
  • To determine the cellular mechanisms underlying ET-mediated angiogenesis, specifically the involvement of leukocytes and specific ET receptors.

Main Methods:

  • Pellets containing varying concentrations of ET-1 or ET-3 were implanted into rat corneal micro-pockets.
  • Murine vascular endothelial growth factor (VEGF) and human interleukin-8 (IL-8) served as positive controls.

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  • Angiogenesis was assessed, and the roles of leukopenia and specific ET receptor antagonists (ET(A), ET(B)) were evaluated.

    • Main Results:

    • Both ET-1 and ET-3 induced significant angiogenesis in the rat cornea, with positive rates of 71% and 72%, respectively.
    • ET-1 and ET-3 mediated angiogenesis was independent of leukopenia (reduced white blood cell count).
    • ET-1-induced angiogenesis was blocked by ET(A) receptor antagonists but not by ET(B) receptor antagonists, indicating ET(A) receptor dependency.

    Conclusions:

    • Endothelins-1 and -3 are direct angiogenic factors in the rat cornea.
    • The pro-angiogenic effect of ET-1 is mediated primarily through the ET(A) receptor.
    • These findings suggest potential therapeutic targets for modulating ocular angiogenesis.