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Endothelin-1 and antiangiogenesis

Stephanie Lankhorst1, A H Jan Danser1, Anton H van den Meiracker2

  • 1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|October 30, 2015
PubMed

Insights

Antiangiogenesis cancer therapy causes side effects like hypertension by activating the endothelin system, not nitric oxide suppression. Blocking endothelin may mitigate these adverse events.

Area of Science:

  • Oncology
  • Cardiovascular Research
  • Nephrology

Background:

  • Antiangiogenesis therapy targeting vascular endothelial growth factor (VEGF) is crucial in cancer treatment.
  • This therapy can cause preeclampsia-like side effects, including hypertension and renal injury.
  • These side effects are linked to nitric oxide (NO) suppression and endothelin system activation.

Purpose of the Study:

  • To investigate the role of the endothelin system versus NO suppression in mediating side effects of antiangiogenesis therapy.
  • To explore the potential of endothelin receptor blockade in managing these adverse events.

Main Methods:

  • Studies utilizing endothelium NO synthase (eNOS)-deficient mice.
  • Pharmacological interventions with endothelin receptor blockers and sildenafil.
  • Comparison with endothelin system activation in preeclamptic women.

Main Results:

  • Evidence suggests the activated endothelin system, not NO suppression, is the primary mediator of side effects from angiogenesis inhibitors.
  • Endothelin system activation in preeclamptic women shares similarities with antiangiogenesis therapy side effects.
  • Endothelin possesses proangiogenic properties.

Conclusions:

  • The endothelin system plays a critical role in the adverse effects of antiangiogenesis cancer treatments.
  • Targeting the endothelin system could be a therapeutic strategy to manage dose-limiting toxicities.
  • Further investigation into endothelin receptor blockade is warranted for patients receiving angiogenesis inhibitors.
Keywords:
angiogenesis inhibitionendothlin-1preeclampsiavascular endothelial growth factor

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