Stimulation of In Vitro Angiogenesis by Tetrahydrobiopterin in Bovine Aortic Endothelial Cells.

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  • Shimizu Shunichi
    Departments of Pathophysiology, School of Pharmaceutical Sciences, Showa University
  • Yasuda Masako
    Departments of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University
  • Ishii Masakazu
    Departments of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University
  • Nagai Tsutomu
    Departments of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University
  • Kiuchi Yuji
    Departments of Pathophysiology, School of Pharmaceutical Sciences, Showa University
  • Yamamoto Toshinori
    Departments of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University

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Abstract

This study examined whether tetrahydrobiopterin (BH4) stimulates angiogenesis by measuring the formation of tube-like structures in vascular endothelial cells. Bovine aortic endothelial cells that were cultured between two layers of collagen type I gel formed tube-like networks. Addition of BH4 or sepiapterin, a precursor of BH4 synthesis, stimulated the formation of tube-like structures. The sepiapterin-stimulated tube formation was completely inhibited by co-treatment with N-acetylserotonin, an inhibitor of sepiapterin reductase. These findings show that BH4 stimulates in vitro angiogenesis in vascular endothelial cells.

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