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Papers In Press, published online ahead of print January 17, 2006
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Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104
Corresponding Author: fbyfield{at}mail.med.upenn.edu
This study investigates the effect of oxidatively modified low density lipoprotein (oxLDL) on the biomechanical properties of human aortic endothelial cells (HAECs). We show that treatment with oxLDL results in a 90% decrease in membrane deformability of HAECs as determined by micropipette aspiration. Furthermore, aortic endothelial cells freshly isolated from hypercholesterolemic pigs (PAECs) were significantly stiffer than cells isolated from healthy animals. Interestingly, oxLDL had no effect on membrane cholesterol of HAECs, but caused disappearance of a lipid raft marker, GM1, from the plasma membrane. Both, an increase in membrane stiffness and a disappearance of GM1 were also observed in cells that were cholesterol depleted by methyl-
Revised on December 27, 2005
Accepted on January 17, 2006
OxLDL increases endothelial stiffness, force generation and network formation
-cyclodextrin (M
CD). Additionally, oxLDL treatment of HAECs embedded within collagen gels resulted in increased gel contraction, indicating an increase in force generation by the cells. This increase in force generation correlated with an increased ability of HAECs to elongate and form networks in a 3D environment. Increased force generation, elongation and network formation was also observed in cholesterol depleted cells. We suggest, therefore, that exposure to oxLDL results in disruption or redistribution of lipid rafts, which in turn induces stiffening of the endothelium, an increase in endothelial force generation and potential for network formation.
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