Abstract-Shear stress regulates endothelial nitric oxide and superoxide (O 2 Ϫ· ) production, implicating the role of NADPH oxidase activity. It is unknown whether shear stress regulates the sources of reactive species production, consequent low-density lipoprotein (LDL) modification, and initiation of inflammatory events. Bovine aortic endothelial cells (BAECs) in the presence of 50 g/mL of native LDL were exposed to (1) pulsatile flow with a mean shear stress ( ave ) of 25 dyne/cm 2 and (2) oscillating flow at ave of 0. After 4 hours, aliquots of culture medium were collected for high-performance liquid chromatography analyses of electronegative LDL species, described as LDL Ϫ and LDL 2Ϫ . In response to oscillatory shear stress, gp91 phox mRNA expression was upregulated by 2.9Ϯ0.3-fold, and its homologue, Nox4, by 3.9Ϯ0.9-fold (PϽ0.05, nϭ4), with a corresponding increase in O 2 Ϫ· production rate. The proportion of LDL Ϫ and LDL 2Ϫ relative to static conditions increased by 67Ϯ17% and 30Ϯ7%, respectively, with the concomitant upregulation of monocyte chemoattractant protein-1 expression and increase in monocyte/BAEC binding (PϽ0.05, nϭ5). In contrast, pulsatile flow downregulated both gp91 phox and Nox4 mRNA expression (by 1.8Ϯ0.2-fold and 3.0Ϯ0.12-fold, respectively), with an accompanying reduction in O 2 Ϫ· production, reduction in the extent of LDL modification (51Ϯ12% for LDL Ϫ and 30Ϯ7% for LDL 2Ϫ ), and monocyte/BAEC binding. The flow-dependent LDL oxidation is determined in part by the NADPH oxidase activity. The formation of modified LDL via O 2 Ϫ· production may also affect the regulation of monocyte chemoattractant protein-1 expression and monocyte/BAEC binding.

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