Shunichi Shimizu (1), Masako Yasuda (2), Masakazu Ishii (2), Tsutomu
Nagai (2), Yuji Kiuchi (1) and Toshinori Yamamoto (2)
Departments of (1) Pathophysiology and (2) Clinical Pharmacy, School
of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku,
Tokyo 142-8555, Japan
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 BH-4 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.
Keywords: Tetrahydrobiopterin, Angiogenesis, Proliferation