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Nitric oxide and carbon monoxide — Two gaseous regulators of vascular endothelial growth factor synthesis

Stickoxid und Kohlenmonoxid — zwei gasförmige Regulatoren der „Vascular Endothelial Growth Factor“-Synthese

  • Main Topics: Biotechnology In Vascular Surgery
  • Published:
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Summary

Background: Vascular endothelial growth factor (VEGF), produced in response to hypoxia or some proinflammatory cytokines, is a fundamental regulator of angiogenesis.

Methods: In this review we describe the reciprocal relationships between VEGF, endothelial nitric oxide synthase (eNOS), and haem oxygenase-1 (HO-1) pathways.

Results: Proangiogenic activities of VEGF depend on the enhanced generation of nitric oxide (NO), a downstream mediator of VEGF signalling in endothelial cells. Additionally, NO can operate upstream of VEGF, inducing its synthesis and producing a positive NO/VEGF feedback involved in regulation of angiogenesis. NO also activates HO-1, the stress inducible enzyme, metabolizing haem to iron, carbon monoxide (CO), and biliverdin. Haem oxygenase generates both inducer (CO) and inhibitor (iron) of VEGF synthesis and can be suggested as an important modulator of NO- and VEGF-mediated activities.

Conclusions: Further studies should elucidate to what extent the by-products of HO activity play a protective or a detrimental role in pathological angiogenesis.

Zusammenfassung

Grundlagen: Der Vascular Endothelial Growth Factor (VEGF) wird als Reaktion auf Hypoxie und einige proinflammatorische Zytokine gebildet und ist ein grundlegender Regulator der Angiogenese.

Methodik: Anhand einer Übersicht werden die verschiedenen Verbindungen zwischen VEGF, eNOS und Hämoxygenase-1 (HO-1)-Stoffwechselwegen beschrieben.

Ergebnisse: Die proangiogenetische Aktivität des VEGF ist von einer verstärkten Bildung von Stickoxid (NO), einem Mediator von VEGF, abhängig. NO kann auch VEGF regulieren, indem es seine Synthese induziert, und eine positive Rückkopplung, die an der Regulation der Angiogenese beteiligt ist, zwischen NO und VEGF entsteht. NO aktiviert auch HO-1, stressinduzierbare Enzyme und metabolisiert Häm zu Eisen, Kohlenmonoxyd und Biliverin. Hämoxygenase bildet sowohl einen Agonist (CO) als auch einen Inhibitor (Eisen) der VEGF-Synthese und könnte deshalb ein wichtiger Modulator der NO- und VEGF-mediierten Vorgänge sein.

Schlußfolgerungen: Weitere Studien werden zeigen, inwieweit Nebenprodukte der HO-Aktivität förderlich oder nachteilig auf eine gestörte Angiogenese wirken.

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Authors and Affiliations

  1. Department of Cell Biochemistry, Institute of Molecular Biology, Jagiellonian University, Gronostajowa 7, PL-30-387, Krakow, Poland

    J. Dulak Ph.D.

  2. Division of Cardiology, University of Innsbruck, Austria

    J. Dulak Ph.D.

  3. Department of Vascular Surgery, University of Vienna, Austria

    Alicja Jozkowicz

  4. Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland

    Alicja Jozkowicz

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Dulak, J., Jozkowicz, A. Nitric oxide and carbon monoxide — Two gaseous regulators of vascular endothelial growth factor synthesis. Eur. Surg. 34, 118–120 (2002). https://doi.org/10.1046/j.1563-2563.2002.02031.x

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  • DOI: https://doi.org/10.1046/j.1563-2563.2002.02031.x

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