Objectives: Endothelial cells and their progenitors play an important role in angiogenesis that is essential for organogenesis and tissue remodelling, as well as for inflammatory responses and carcinogenesis in all periods of life. In the present study, the authors concentrated on the direct effect of beta-carotene (BC) on human umbilical cord-originated endothelial progenitor cells and human umbilical vein endothelial cells.
Methods: BC uptake was measured using high-performance liquid chromatography. The effect on cell proliferation was measured based on bromodeoxyuridine incorporation. Chemotaxis was performed in a Boyden chamber. The influence on tubular-like structure formation was investigated using a three-dimensional assay in Matrigel (Becton Dickinson, USA) both in an in vitro and in vivo model. Changes in gene expression were analyzed using the microarray hybridization method. Quantitative gene expression was estimated using the real-time polymerase chain reaction method.
Results: It was shown that BC, in the physiological range of concentrations found in human blood, is a potent activator of chemotaxis of endothelial cells. Microarray data analysis revealed that the genes involved in cell-cell and cell-matrix adhesion, matrix reorganization and activation of chemotaxis were the most affected by BC genes in human umbilical vein endothelial cells and endothelial progenitor cells. These results were also confirmed in an in vivo angiogenesis model.
Conclusion: BC, in the range of physiological concentrations, stimulates early steps of angiogenic activity of endothelial cells by activation of cellular migration, as well as by matrix reorganization and a decrease in cellular adhesion.
Keywords: Angiogenesis; Beta-carotene; Chemotaxis; Endothelium; Microarray.