1519 Pure Appl. Chem., Vol. 78, No. 8, pp. 1519–1537, 2006. doi:10.1351/pac200678081519 © 2006 IUPAC -Carotene and angiogenesis* Aldona Dembi´ nska-Kie´ c 1,‡ , Malgorzata Malczewska-Malec 1 , Anna Polus 1 , Beata Kie´ c-Wilk 1 , Joanna Grzybowska 1 , Jerzy Stachura 2 , Grzegorz Dyduch 2 , Julian Pryjma 3 , Joanna Skrzeczy´ nska 3 , Thomas Langman 4 , Marek Bodzioch 1 , L / ukasz Partyka 1 , and Gerd Schmitz 4 1 Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland; 2 Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland; 3 Department of Immunology, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland; 4 Department of Clinical Chemistry, Laboratory Medicine and Transfusiology, University of Regensburg, Regensburg, Germany Abstract: 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 in- flammatory 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 pro- liferation 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/ma- trix adhesion, matrix reorganization, G-protein-regulated intracellular signaling as well as genes involved in the rapid remodeling of the actin cytoskeleton. We conclude that physio- logical 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 adhe- sion. Keywords: β-carotene; angiogenesis; endothelium; microarrays; chemotaxis. INTRODUCTION Vasculogenesis and angiogenesis play essential roles in a number of physiologic and pathologic events, such as fetal development, vascular remodeling of growth, ischemia, inflammation, diabetic retinopa- thy, as well as progression of growth and invasiveness of solid tumors [1]. Carotenoids, retinol, and *Paper based on a presentation at the 14 th International Symposium on Carotenoids, Edinburgh, Scotland, 17–22 July 2005. Other presentations are published in this issue, pp. 1477–1557. ‡ Corresponding author: Address: Kopernika 15a, 31-501 Krakow, Poland; Tel.: +48 12 421 40 06; Fax: + 48 12 421 40 73; E-mail: mbkiec@cyf-kr.edu.pl