Stimulation of Human Endothelial Cells by Amino Acids: Expression of Nitric Oxide Synthases and Endothelial Growth Factors

Abstract

Background/Aims: The complex process of fracture healing relies on the reciprocal action of microvascular endothelial cells and osteoblasts. We hypothesized that, in addition to revascularization, stimulated microendothelial cells secrete growth factors known to influence osteoblasts in vitro and in animal trials. Methods: The study describes the effect of L-glycine, L-arginine, and L-lysine on human microvascular endothelial cells (HDMEC) with respect to the in-vitro expression of basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), and endothelial and inducible nitric oxide synthases (e-NOS, i-NOS). The amino acids were added on day 0, and b-FGF, VEGF, e-NOS, and i-NOS were measured by ELISA on days 0, 1, 3, and 6. Results: The number of HDMEC was not significantly influenced by the addition of amino acids, suggesting that the observed effects were not related to proliferation. HDMEC immediately released b-FGF into the cellular supernatant when L-glycine was added. In addition, HDMEC were stimulated to produce i-NOS and e-NOS after a single addition of L-arginine. Conclusion: These findings suggest that L-arginine and L-glycine stimulate HDMEC to express NOS and b-FGF, compounds well-known for their osteoblast modulating activities. If confirmed in animal studies, supplementation with L-arginine or L-glycine may be an attractive therapeutic approach to enhance fracture repair.

Key words

L-arginine - L-glycine - human microvascular endothelial cells - fracture healing

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