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