Oligomeric procyanidins inhibit cell migration and modulate the expression of migration and proliferation associated genes in human umbilical vascular endothelial cells

Abstract

The consumption of flavan-3-ols has been associated with reduced risk of cardiovascular diseases and improvements in vascular function. However, the nature of the flavan-3-ols responsible and the mechanisms underlying the vascular responses are not fully understood. We used microarrays to search for molecular changes in response to the exposure to (-)-epicatechin (EC), procyanidin dimer B2, and a mixture of oligomeric procyanidins in human umbilical vein endothelial cells (HUVECs). No gene expression changes were detected in HUVECs exposed to EC or dimer B2, however, the oligomeric procyanidins induced significant gene expression changes in both resting and TNF-alpha-stimulated cells. In particular, the expression of genes such as ADAMTS1, THBS1, ANGPT2, CYR61, ET-1, EDG3, and PDE4B involved in endothelial cell migration and proliferation, were substantially over-represented. Also, exposure to the oligomers arrested the cells at the G(0)/G(1 )phase and inhibited cell migration. These data show that human endothelial cells respond to oligomeric procyanidins by exhibiting a less migratory phenotype and by a general modulation of the expression of genes that are associated with key events in the angiogenic process. The molecular changes associated with procyanidin treatment identified in this study are consistent with the beneficial effects of flavan-3-ols on vascular function.