OxLDL Facilitates Flow-induced Realignment of Aortic Endothelial Cells

Alignment of vascular endothelial cells (ECs) in the direction of the flow is considered a key factor in maintaining endothelial integrity in an active hemodynamic environment. Our recent studies showed that exposure to oxidized LDL (oxLDL), one of the major proatherogenic lipoproteins, significantly increases the stiffness of human aortic ECs, suggesting that oxLDL may have a significant impact on the sensitivity of ECs to mechanical stimuli. In this study, we show that oxLDL strongly enhances the ability of ECs to realign in the direction of the flow and facilitates the formation of F-actin stress fibers under static and flow conditions. The impact of oxLDL on the flow-induced realignment is observed on whole cell and single-fiber levels. We also show that, similar to the effect of oxLDL on endothelial stiffness, the impact of oxLDL on flow-induced realignment can be simulated by methyl-beta-cyclodextrin-induced cholesterol depletion, supporting the hypothesis that oxLDL acts as cholesterol acceptor, rather than cholesterol donor, for ECs. Finally, we propose that oxLDL/cholesterol depletion-induced sensitization of ECs to flow may be a result of an increase in cellular stiffness and a respective increase in membrane-cytoskeleton tension.