Laktat stimuliert die Migration von humanen Endothelzellen Lactate enhances migration of human endothelial cells

Introduction: Healing wounds are characterized by high lactate levels. Lactate has been shown to enhance collagen synthesis by fibroblasts and VEGF production by macrophages. However, little is known whether the increased VEGF level correlates with enhanced biological activity. Therefore, we investigated the migration of endothelial cells treated with lactate. Material and methods: Human umbilical vein endothelial cells (HUVEC) were cultured to subconfluent monolayers in standard 6 well tissue culture plates. Following a 16 hour serum starvation period, cells were treated with indicated concentrations of lactate for 20 hours in a standard incubator at 95 % air and 10 % CO2. Cellular migration was assessed using a modified Boyden-chamber. VEGF protein in the cell culture supernatant was measured by ELISA. All experiments were performed in triplicates and repeated at least twice. Results are given as mean + SD; a p-value less than 0.05 calculated by Student’s t-test was considered significant. Results: Lactate enhanced VEGF protein synthesis in a time- and dose-dependent manner. Lactate added to the bottom well did not stimulate cellular migration from the upper well. However, lactate together with endothelial cells in the bottom well of the Boyden-Chamber increased cellular migration in a dose-dependent manner. This effect could be blocked both by anti-VEGF or cyclohexamide as well. Conclusion: Lactate enhances VEGF production in human endothelial cells. However, lactate is not a chemoattractant. Lactate mediated increase in cellular migration is regulated by VEGF.