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Endotheliitis, endothelin, and endothelin receptor blockers in COVID-19

Devang K Sanghavi1, Anoop Titus2, Thomas R Caulfield3

  • 1Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL, United States.

Medical Hypotheses
|April 6, 2021
PubMed

Insights

Endothelin contributes to COVID-19 complications by causing inflammation and vasoconstriction. Endothelin receptor blockers may offer a potential therapeutic strategy for treating coronavirus disease 2019 (COVID-19).

Area of Science:

  • Cardiovascular Research
  • Infectious Diseases
  • Pathophysiology

Background:

  • Endothelin is a potent vasoconstrictor, pro-inflammatory, and pro-oxidative agent.
  • Endotheliitis, inflammation of the endothelium, is implicated in coronavirus disease 2019 (COVID-19) pathophysiology.
  • Endothelial dysfunction contributes to end-organ damage in COVID-19.

Purpose of the Study:

  • To summarize the role of endothelin in COVID-19.
  • To highlight endotheliitis as a key pathophysiologic process in COVID-19.
  • To explore the potential of endothelin receptor blockers as COVID-19 therapies.

Main Methods:

  • Literature review and summary of existing research on endothelin and COVID-19.
  • Analysis of the pathophysiologic mechanisms linking endothelin to COVID-19 end-organ dysfunction.
  • Discussion of the therapeutic potential of endothelin receptor antagonists.

Main Results:

  • Endothelin exacerbates COVID-19 through vasoconstriction, inflammation, and oxidative stress.
  • Endotheliitis is a significant factor in COVID-19-related dysfunction of the heart, lungs, kidneys, and brain.
  • Endothelin receptor blockers (e.g., bosentan, sitaxentan) show promise in preclinical contexts.

Conclusions:

  • Endothelin plays a critical role in the multifaceted pathology of COVID-19.
  • Targeting endothelin signaling via receptor blockers presents a potential therapeutic avenue for COVID-19.
  • Further clinical trials are warranted to establish the efficacy of endothelin receptor blockers in treating COVID-19.

Keywords:
BosentanCOVID-19EndotheliitisEndothelinEndothelin receptor blockersSitaxentan

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