cDNA microarray analysis of the gene expression profile of VEGF-activated human umbilical vein endothelial cells.

Vascular endothelial growth factor (VEGF) is one of the most important factors that stimulate angiogenesis and vascular permeability. To clarify the role of VEGF, we analysed a human cDNA chip containing 7267 human genes to identify genes induced by VEGF in human umbilical vein endothelial cells (HUVECs). One hundred thirty-nine cDNAs, including ninety-nine previously known and forty poorly characterized or novel sequences, were increased more than two-fold by VEGF within twenty-four hours of stimulation. Among them, only five are known to regulate angiogenesis: cyclooxygenase 2 (COX2), heparin-binding epidermal growth factor-like growth factor, early growth response 1 (EGR 1), CYR61, and angiopoietin 2. Fifty-three genes induced within the first two hours were thought to be directly induced by VEGF. Of these, Down syndrome candidate region 1 (maximum induction = 6.1-fold) was the most profoundly induced, followed by Mifl (KIAA0025; 5.5-fold), COX2 (4.7-fold), EGR 3 (3.7-fold), EGR 2 (3.2-fold), bactericidal/permeability-increasing protein (3.1-fold), and CD1B antigen, b polypeptide (3.1-fold). In addition to the genes mentioned above, there were many poorly characterized or novel genes induced by VEGF. Further analysis of these genes may aid in the elucidation of the molecular mechanisms of angiogenesis or vascular permeability stimulated by VEGF.