β-Carotene and angiogenesis
Carotenoids and retinoids modulate growth and differentiation of a variety of cell types and are fundamental regulators of development. Endothelial cells play an important role in angiogenesis, which is essential for organogenesis and tissue remodeling, but also inflammatory response or carcinogenesis. Binding to the retinoid (RARs) or rexinoid (RXRs) receptors, all-trans-RA, 13-cis-RA, 9-cis-RA, and synthetic retinoids and rexinoids showed antiangiogenic properties in several models. However, the role of β-carotene in endothelial cell function and angiogenesis is still poorly characterized. Although in our experiments, β-carotene used in nontoxic concentrations (up to 3 μM) had no detectable effect on the proliferation or apoptosis of HUVECs or umbilical-cord-blood-derived endothelial progenitors; β-carotene did not change the tubulogenic activity of cells in an in vitro angiogenesis model, but it potently activated the migration of endothelial and progenitor cells. β-Carotene also promoted the development of microcapillaries in a matrigel plug injected subcutaneously into mice. The analysis of microarray data from endothelial cells revealed that β-carotene modified the expression of genes involved in activation of chemotaxis, cell/cell and cell/matrix adhesion, matrix reorganization, G-protein-regulated intracellular signaling as well as genes involved in the rapid remodeling of the actin cytoskeleton. We conclude that physiological levels of β-carotene stimulate early steps of angiogenic activity of endothelial cells by activation of cellular migration as well as matrix reorganization and reduction of cell adhesion.