Fluid Flow Inhibits Endothelial Adhesiveness Nitric Oxide and Transcriptional Regulation of VCAM-1

Background In the arterial tree, regions exposed to reduced shear stress (low and/or disturbed flow) are predisposed to atherogenesis. Fluid flow is a potent stimulus for the release of endothelium-derived nitric oxide (NO). Because NO inhibits monocyte–endothelial cell interaction, we speculated that the effects of flow in inhibiting atherogenesis might be mediated in part by NO. Methods and Results Confluent monolayers of human aortic endothelial cells were exposed to static or fluid flow conditions for 4 hours. The medium was replaced, and cells were then incubated with native LDL (50 μg/mL), oxidized LDL (30 μg/mL), or lipopolysaccharide (LPS) (10 ng/mL) + tumor necrosis factor-α (TNF-α) (10 U/mL) for an additional 4 hours. Functional binding assays using THP-1 monocytes were then performed. Superoxide production by human aortic endothelial cells was monitored by lucigenin chemiluminescence, and expression of the adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion ...