Effects of folate deficiency on endothelial cell biology: Folate deficiency induces profound effects on global patterns of gene expression in vascular endothelial cells

Folate deficiency is an independent risk factor for atherosclerotic cardiovascular disease. The hypothesis that folate deficiency directly affects endothelial cells has never been tested. To better understand how folate deficiency elicits changes in vascular wall homeostasis, we characterized an in vitro model of endothelial cell folate deficiency using human umbilical vein endothelial cells (HUVECs). We conducted global gene expression analysis to address the effects of folate deficiency on endothelial cell gene expression. Severe folate deficiency, induced the classic response of reduced cell growth induced, by an intra S-phase cell cycle arrest, and increased cell volume. Primary endothelial cells were found to be sensitive to physiological levels of folate at a concentration of 40 nM (within the normal range in humans) and respond by exhibiting an inflammatory response as evidenced by the changes in expression of IL-8, CXCL1, ICAM1, COX-1 and COX-2. These changes are characteristic of the activated endothelium.